Peptides (v.28, #7)

Studies conducted on amphibian skin secretions over the past 40 years have isolated and identified huge arrays of bioactive peptides, many of which have demonstrated potent anti-microbial activity. Such peptides are attracting increasing attention due to the growing problem of pathogenic microorganisms resistant to conventional antibiotics. The current study utilized a combined proteomic/genomic approach to facilitate the high throughput sequencing of five novel dermaseptins and four novel phylloseptins from the skin secretions of Phyllomedusa hypochondrialis azurea. Peptides were partially identified using Q-TOF MS/MS fragmentation and de novo sequencing, while a cDNA library was constructed from the lyophilized skin secretion. 3′-RACE reactions used primers designed for the highly conserved 5′-signal regions of previously deduced dermaseptin precursors. cDNA sequenced peptides were attributed to their respective fragmentation spectra to confirm the structure of the final processed peptides. Such an approach identified post-translational modifications in addition to deciphering isobaric amino acids. Several of the peptides were purified to homogeneity and displayed potent antimicrobial activity with minimum inhibitory concentrations starting at 0.4 μM when tested against and range of Gram-positive and Gram-negative bacteria including Escherichia coli, Staphylococcus aureus and Micrococcus luteus.
Keywords: De novo peptide sequencing; Amphibian skin secretion; Antimicrobial peptide; Phyllomedusa hypochondrialis azurea; cDNA cloning;

A new cyclic lipopeptide (CLP) purified from Bacillus subtilis natto T-2 dose dependently inhibited growth in human leukemia K562 cells. The results of fluorescent staining indicated that CLP brought about apoptosis in K562 cells. Flow cytometric analysis also demonstrated that CLP caused dose-dependent apoptosis of K562 cells through cell arrest at G1 phase. Western blotting revealed that CLP-induced apoptosis in K562 cells was associated with caspase-3 and poly(ADP-ribose)polymerase (PARP) protein. It is estimated that CLP inhibited proliferation in K562 cells by inducing apoptosis.
Keywords: Apoptosis; Human leukemia K562 cells; Cyclic lipopeptide (CLP); Anti-tumor;

New Trichobrachins, 11-residue peptaibols from a marine strain of Trichoderma longibrachiatum by Nicolas Ruiz; Gaëtane Wielgosz-Collin; Laurence Poirier; Olivier Grovel; Karina Ethel Petit; Mustapha Mohamed-Benkada; Thibaut Robiou du Pont; John Bissett; Philippe Vérité; Gilles Barnathan; Yves François Pouchus (1351-1358).
A marine strain of Trichoderma longibrachiatum isolated from blue mussels (Mytilus edulis) was investigated for short peptaibol production. Various 11-residue peptaibols, obtained as microheterogenous mixtures after a chromatographic fractionation, were identified by positive mass spectrometry fragmentation (ESI-IT-MSn, CID-MSn and GC/EI-MS). Thirty sequences were identified, which is the largest number of analogous sequences so far observed at once. Twenty-one sequences were new, and nine others corresponded to peptaibols already described. These peptaibols belonged to the same peptidic family based on the model Ac-Aib-xxx-xxx-xxx-Aib-Pro-xxx-xxx-Aib-Pro-xxol. They were named trichobrachin A when the residue in position 2 was an Asn, and trichobrachin C when it was a Gln. Major chromatographic sub-fractions, corresponding to purified peptaibols, were assayed for their cytotoxic activity. Trichobrachin A-IX and trichobrachin C exhibited the highest activities. There was an exponential relation between their relative hydrophobicity and their cytotoxicity on KB cells.
Keywords: Marine fungi; Trichoderma longibrachiatum; 11-Residue peptaibols; Mass spectrometry; Microheterogeneity; Cytotoxicity; Hydrophobicity; Trichobrachin A; Trichobrachin C;

Two novel octapeptide members of the AKH/RPCH family have been identified from the corpora cardiaca (CC) of two species of water bugs. The giant water bug Lethocerus indicus (family: Belostomatidae) contains a peptide code-named Letin-AKH with the sequence pGlu-Val-Asn-Phe-Ser-Pro-Tyr-Trp amide, and the water scorpion Nepa cinerea (family: Nepidae) has the peptide code-named Nepci-AKH with the sequence pGlu-Leu/Ile-Asn-Phe-Ser-Ser-Gly-Trp amide. The sequences were deduced from the multiple MS N electrospray mass data from crude CC extracts. Synthetic peptides were made and co-elution on reversed-phase high performance liquid chromatography (RP-HPLC) with the natural peptide from crude gland extract confirmed the accuracy of the deduced sequence for Letin-AKH and demonstrated that Nepci-AKH contains a Leu residue at position 2 and not an Ile residue. A previously characterized member of the AKH/RPCH family was identified in the stick water scorpion Ranatra linearis by mass spectrometry: Grybi-AKH (pGlu-Val-Asn-Phe-Ser-Thr-Gly-Trp amide) has the same mass (919 Da) as Nepci-AKH and differs in two positions from Nepci-AKH (residues 2 and 6). The apparent function of the peptides is to achieve lipid mobilization in the species under investigation; indications for this came from conspecific bioassays using the appropriate synthetic peptides for injecting into the insects. This function is very likely linked to dispersal flight metabolism of water bugs. Swimming activity in N. cinerea also results in an increase in lipid concentration in the hemolymph.
Keywords: Insects; Heteroptera; Water bugs; AKH/RPCH family; Mass spectrometry; Phylogeny;

Evidence for an angiotensin-converting enzyme (ACE) polymorphism in the crayfish Astacus leptodactylus by Nédia Kamech; Juraj Simunic; Sen Jeanne Franklin; Sophie Francis; Maria Tabitsika; Daniel Soyez (1368-1374).
The present study was initiated to characterize angiotensin-converting enzyme (ACE) in Crustaceans. Using degenerate DNA primers deduced from consensus sequences located upward and downward from the active site of ACEs from different arthropod species, several tissues from the crayfish Astacus leptodactylus were screened by RT-PCR. Amplicons were obtained from hepatopancreas, testis and hemocytes. Analysis of the predicted protein sequences after cloning and Northern blot experiments revealed an original and complex polymorphism of the ACE-like active site. Two variants were obtained in the hepatopancreas, one displaying a 6.4 kb size transcript, probably corresponding to a double domain ACE, with an unusual active site structure while the other had a transcript size of 2.5 kb, close to the size of the transcript obtained in testis and hemocytes (2 and 3 kb, respectively), likely representing single domain enzymes. Functional assays using a synthetic substrate were performed from the different tissues and showed a maximal ACE-like activity associated to membrane fraction from testis and hepatopancreas.
Keywords: Angiotensin-converting enzyme; Zinc-metallopeptidase; Peptide substrate; Crustacean; Crayfish;

Evidence for a role of AT2 receptors at the CVLM in the cardiovascular changes induced by low-intensity physical activity in renovascular hypertensive rats by M.C. Rodrigues; M.J. Campagnole-Santos; R.P. Machado; M.E. Silva; J.L.M. Rocha; P.M. Ferreira; R.A.S. Santos; A.C. Alzamora (1375-1382).
In the present study, we evaluated the involvement of the rennin–angiotensin system (RAS) in the control of the blood pressure (BP), baroreceptor-mediated bradycardia and the reactivity of caudal ventrolateral medulla (CVLM) neurons to Ang II and to AT2 receptor antagonist in sedentary or trained renovascular hypertensive rats. Physical activity did not significantly change the baseline mean arterial pressure (MAP), heart rate (HR) or the sensitivity of the baroreflex bradycardia in normotensive Sham rats. However, in 2K1C hypertensive rats, physical activity induced a significant fall in baseline MAP and HR and produced an improvement of the baroreflex function (bradycardic component). The microinjections of Ang II into the CVLM produced similar decreases in MAP in all groups, Sham and 2K1C, sedentary and trained rats. The hypotensive effect of Ang II at the CVLM was blocked by previous microinjection of the AT2 receptors antagonist, PD123319, in all groups of rats. Unexpectedly, microinjection of PD123319 at the CVLM produced a depressor effect in 2K1C sedentary that was attenuated in 2K1C trained rats. No significant changes in MAP were observed after PD123319 in Sham rats, sedentary or trained. These data showed that low-intensity physical activity is effective in lowering blood pressure and restoring the sensitivity of the baroreflex bradycardia, however these cardiovascular effects are not accompanied by changes in the responsiveness to Ang II at CVLM in normotensive or hypertensive, 2K1C rats. In addition, the blood pressure changes observed after AT2 blockade in 2K1C rats suggest that hypertension may trigger an imbalance of AT1/AT2 receptors at the CVLM that may be restored, at least in part, by low-intensity physical activity.
Keywords: Caudal ventrolateral medulla; Baroreflex control of heart rate; Angiotensin II; Low-intensity physical activity; Renovascular hypertension (2K1C);

We investigated the role of kinin receptors in cardiac remodeling after ischemia/reperfusion (I/R). Bradykinin injection improved cardiac contractility, diastolic function, reduced infarct size and prevented left ventricular thinning after I/R, whereas des-Arg9-BK injection had no protective effects. Bradykinin, but not des-Arg9-BK, reduced cardiomyocyte apoptosis and increased Akt and GSK-3β phosphorylation. Furthermore, myocardial infarct size was similar between wild type and B2 knockout mice after I/R, but significantly reduced in kinin B1 receptor knockout mice. These results indicate that the kinin B2 receptor, but not the B1 receptor, protects against I/R-induced cardiac dysfunction by inhibiting apoptosis and limiting ventricular remodeling.
Keywords: B1 receptor; B2 receptor; Bradykinin; Ischemia/reperfusion; Remodeling;

Sequencing and cardiac expression of natriuretic peptide receptor 2 (NPR-B) in Sus Scrofa by Silvia Del Ry; Manuela Cabiati; Vincenzo Lionetti; Chiara Colotti; Maristella Maltinti; Michele Emdin; Fabio A. Recchia; Daniela Giannessi (1390-1396).
Keywords: Natriuretic peptide receptor-B; Sus Scrofa; mRNA; Cardiac tissue;

Diadenosine tetraphosphate stimulates atrial ANP release via A1 receptor: Involvement of KATP channel and PKC by Kuichang Yuan; Chunhua Cao; Guang Yi Bai; Sung Zoo Kim; Suhn Hee Kim (1397-1405).
Diadenosine polyphosphates (APnAs) are endogenous compounds and exert diverse cardiovascular functions. However, the effects of APnAs on atrial ANP release and contractility have not been studied. In this study, the effects of diadenosine tetraphosphate (AP4A) on atrial ANP release and contractility, and their mechanisms were studied using isolated perfused rat atria. Treatment of atria with AP4A resulted in decreases in atrial contractility and extracellular fluid (ECF) translocation whereas ANP secretion and cAMP levels in perfusate were increased in a dose-dependent manner. These effects of AP4A were attenuated by A1 receptor antagonist but not by A2A or A3 receptor antagonist. Other purinoceptor antagonists also did not show any effects on AP4A-induced ANF release and contractility. The increment of ANP release and negative inotropy induced by AP4A was similar to those induced by AP3A, AP5A, and AP6A. Protein kinase A inhibitors accentuated AP4A-induced ANP secretion. In contrast, an inhibitor of phospholipase C, protein kinase C or sarcolemma KATP channel completely blocked AP4A-induced ANP secretion. However, an inhibitor of adenylyl cyclase or mitochondria KATP channel had no significant modification of AP4A effects. These results suggest that AP4A regulates atrial inotropy and ANP release mainly through A1 receptor signaling involving phospholipase C-protein kinase C and sarcolemmal KATP channel and that protein kinase A negatively modulates the effects of AP4A.
Keywords: Diadenosine polyphosphate; Adenosine; ATP; Purinoceptor; Atrial natriuretic peptide; Atrial contractility; cAMP; KATP channel;

Corticotropin-releasing factor (CRF)-induced behaviors are modulated by intravenous administration of teneurin C-terminal associated peptide-1 (TCAP-1) by Arij Al Chawaf; Karen Xu; Laura Tan; Franco J. Vaccarino; David A. Lovejoy; Susan Rotzinger (1406-1415).
The teneurin C-terminal associated peptides (TCAP) are a recently discovered family of bioactive peptides that can attenuate aspects of the behavioral stress responses of rats. Because TCAP has some structural similarity to the corticotropin-releasing factor (CRF) family of peptides, and modulates elements of the stress response, TCAP may act to modulate CRF actions in vivo. This hypothesis was tested by investigating anxiety-related behaviors in male rats following repeated intravenous (IV) TCAP-1 administration with either an acute intracerebroventricular (ICV) or IV CRF challenge. TCAP-1 alone did not affect behavioral responses significantly, however did significantly affect CRF-regulated behaviors depending on CRF's mode of injection. In both the elevated plus-maze and the open field tests, TCAP-1 had an anxiolytic effect on ICV CRF responses as indicated by decreased stretched-attend postures in the elevated plus maze (p  < 0.05), and increased center time and center entries in the open field (p  < 0.05). However, prior TCAP-1 treatment has an anxiogenic effect on the IV CRF-induced behaviors (decreased center entries and total distance in the open field (p  < 0.05)). TCAP-1's actions are not mediated through acute changes in glucocorticoid levels and may occur via a central action in the brain. A fluorescently (FITC)-labeled TCAP-1 analog was IV-administered to investigate whether IV TCAP-1 has the potential to regulate central mechanisms by crossing the blood–brain barrier. FITC-TCAP-1 was detected in blood vessels and fibers in the brain indicating that uptake into the brain is a possible route for its interaction with CRF and its receptors. Thus, TCAP may modulate CRF-associated behaviors by a direct action in the CNS.
Keywords: Anxiety; Behavior; Corticotropin-releasing factor (CRF); Teneurin; Blood–brain barrier;

Islet amyloid polypeptide (IAPP) is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and reduce adipose energy reserves. The present study compared the effects of chronic peripheral and chronic central administration of IAPP on food intake and meal pattern in rats. IAPP was administered subcutaneously (SC) for 7 days at doses of 0, 0.25, 2.5 and 25 pmol kg−1  min−1 using an osmotic minipump or administered centrally at doses of 0, 0.025, 0.25 and 2.5 pmol kg−1  min−1 using an osmotic minipump connected to an intracerebroventricular (ICV) catheter inserted into the third ventricle. Both SC and ICV infusion decreased total food intake dose-dependently. The minimal effective dose was 2.5 pmol IAPP kg−1  min−1 for SC administration and 0.25 pmol kg−1  min−1 for ICV infusion. The decrease in food intake produced by infusion of IAPP was mainly due to decreased meal size, although a significant decrease in meal number also occurred at the highest SC and ICV doses. SC administration produced a larger, more persistent decrease in food intake during the light period than in the dark period, while ICV infusion caused a larger, more persistent decrease during the dark period. The 10-fold difference in minimal effective doses indicates that ICV-administered IAPP acted primarily in the brain to inhibit food intake. The difference between the effects of IAPP on meal pattern with the two methods of administration suggests that IAPP does not act on the same target(s) when administered centrally as it does when it is administered peripherally.
Keywords: Amylin; Body weight; Food intake; Meal pattern; Satiety;

Copper complexing decreases the ability of amyloid beta peptide to cross the BBB and enter brain parenchyma by Suneetha Mare; Suman Penugonda; Sandra M. Robinson; Shinya Dohgu; William A. Banks; Nuran Ercal (1424-1432).
The amyloid hypothesis states that amyloid beta protein (Aβ) plays a major causal role in the onset of Alzheimer's disease. Toxicity of Aβ can be modified by metal ions. Two mechanisms by which such Aβ and metal ions could interact are by enhanced oxidative stress or by altered fibrillation. Specifically, Aβ fibrillation is increased by aluminum (Al) and copper (Cu) and Al also increases Aβ uptake into brain. Here, we determined whether chelation with Cu would alter uptake of the human or rat 1-42 form of Aβ (Aβ42) by brain or alter Aβ-induced oxidative stress in an immortalized line of rat brain endothelial cells (RBE4). We found that Cu enhanced cytotoxicity of rat, but not of human Aβ, had no effect on glutathione (GSH) or cysteine (CYS) levels. Cu significantly decreased homocysteine (HCYS) levels when complexed with Aβ. Cu chelation did not alter Aβ uptake into brain or other tissues (except for kidney) or alter clearance from blood or brain in vivo, but did increase efflux in an in vitro model of the blood–brain barrier (BBB). Chelation to Cu also impaired the capillary to brain transport of Aβ, an effect opposite to that previously found for chelation of Aβ to Al. These results show that metal ions have varied effects on Aβ uptake by brain and that Cu could be protective against the neurotoxic effects of circulating Aβ.
Keywords: Alzheimer's disease; Amyloid beta peptide; Copper; BBB;

Levels of neuropeptides nocistatin, nociceptin/orphanin FQ and their precursor protein in a rat neuropathic pain model by Tessy Joseph; Tat-Leang Lee; Chunmei Li; Chiang Siau; Yuji Nishiuchi; Terutoshi Kimura; Shinro Tachibana (1433-1440).
Neuropeptides nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are related to pain modulation. The amounts of these peptides and their precursor protein, prepronociceptin (ppN/OFQ) in the brain, spinal cord and serum samples of rats with partial sciatic nerve ligation (PSNL) were compared with those in naïve rats using radioimmunoassay (RIA). There was a significant rise in the levels of ppN/OFQ, N/OFQ and NST in the brains of PSNL rats. Their spinal cords showed significantly increased ppN/OFQ and NST levels but no change in N/OFQ levels. The PSNL rats also had increased serum NST (statistically significant) and N/OFQ (statistically insignificant) with decreased ppN/OFQ suggesting important roles of these peptides in neuropathic pain mechanism.
Keywords: Nociceptin/orphanin FQ; Nocistatin; Prepronociceptin; Neuropathic pain; Radioimmunoassay;

Blockade of the nociceptin/orphanin FQ/NOP receptor system in the rat ventrolateral periaqueductal gray potentiates DAMGO analgesia by Giovanna M. Scoto; Giuseppina Aricò; Simone Ronsisvalle; Carmela Parenti (1441-1446).
Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in various biological functions including pain. High density of NOP receptor has been found in the ventrolateral periaqueductal gray (vlPAG), the main output pathway involved in descending pain-control system. The aim of our work was to evaluate the involvement of the N/OFQ/NOP system in the modulation of MOP analgesia in the rat vlPAG using UFP-101, a selective NOP antagonist. N/OFQ significantly blocked DAMGO (a selective MOP agonist) analgesia, while UFP-101 enhanced the effect of the opioid given at a subanalgesic dose. These results confirm our hypothesis of an antiopioid role for N/OFQ in the vlPAG.
Keywords: vlPAG; N/OFQ; UFP-101; DAMGO; Pain;

A gastrin-releasing peptide receptor antagonist blocks d-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats by Márcia Kauer-Sant’Anna; Ana Cristina Andreazza; Samira S. Valvassori; Márcio Rodrigo Martins; Luciana M. Barbosa; Gilberto Schwartsmann; Rafael Roesler; João Quevedo; Flávio Kapczinski (1447-1452).
The gastrin-releasing peptide receptor (GRPR) has emerged as a novel molecular target in neurological and psychiatric disorders, and previous animal studies suggest that GRPR antagonists might display cognitive-enhancing and antipsychotic properties. Hyperlocomotion produced by administration of d-amphetamine (d-AMPH) to rats has been put forward as a model of the manic phase of bipolar disorder (BD). In the present study, we examined the effects of a single systemic administration of the GRPR antagonist [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6–14) (RC-3095) on hyperlocomotion induced by a single systemic injection of d-AMPH in male rats. We also evaluated the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of rats treated with d-AMPH and RC-3095. Administration of RC-3095 at any of the doses used blocked d-AMPH-induced hyperlocomotion. Specific doses of RC-3095 increased the levels of NGF and BDNF in the dorsal hippocampus. Administration of d-AMPH did not affect NGF or BDNF levels by itself, but blocked the RC-3095 effects. The results suggest that GRPR antagonists might display anti-manic activity.
Keywords: Bombesin-like peptides; Gastrin-releasing peptide receptor; RC-3095; NGF; BDNF; Bipolar disorder;

Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis by Jen Chang; Julia J. Hoy; Prema S. Idumalla; Matthew S. Clifton; Norman C. Pecoraro; Aditi Bhargava (1453-1460).
It is becoming increasingly evident that the urocortins (Ucns) and their receptors are involved in the initiation and development of inflammation in the gastrointestinal (GI) tract. There has not been a systematic study of the basal expression of Ucns or their receptors in the GI tract. Here, we examined basal expression of Ucn 2 and its high-affinity receptor, CRF-R2 in the rat GI tract. Ucn 2 mRNA was expressed throughout the small and large intestine. Surprisingly, CRF-R2 mRNA expression was detected in only a subset of GI regions that expressed Ucn 2. Immunohistochemical study showed that both Ucn 2 immuno-reactivity (Ucn 2-IR) and CRF-R2-IR were consistently seen in the neurons of the myenteric plexus and the nerve fibers innervating the circular muscle. By and large, Ucn 2-IR was detected in all layers, including the mucosal and the submucosal layers throughout the GI regions. In contrast, CRF-R2-IR was very low or undetectable in the mucosal layers of all regions examined. The role of Ucn 2 and CRF-R2 was then examined in a rat model of chemically-induced colitis. In the early phase of colitis, Ucn 2 mRNA levels peaked, whereas, in striking contrast, CRF-R2 mRNA expression decreased ∼2.5-fold below control levels. At the peptide level, Ucn 2-IR was specifically induced in a large population of immune cells that infiltrated the lamina propria and submucosa of the distal colon, whereas CRFR2-IR was detected in only a small fraction of infiltrated immune cells. CRF-R2-IR was dramatically reduced in the neurons of the myenteric plexus. Thus, we show, for the first time, that in the acute phase of inflammation, Ucn 2 levels are increased whereas expression levels of its only identified receptor, CRF-R2, are decreased. This suggests that Ucn 2 exerts its effects only in part via CRF-R2.
Keywords: Urocortin 2; Corticotropin-releasing factor receptor 2; Inflammation; Cytokine; Rat; gastrointestinal tract; Immunohistochemistry;

Copper-binding activity of Trefoil factor 1 (TFF1): A new perspective in the study of the multifunctional roles of TFFs by Alessandra Tosco; Maria Chiara Monti; Bianca Fontanella; Marie-Christine Rio; Luigi Gomez-Paloma; Arturo Leone; Liberato Marzullo (1461-1469).
Trefoil factors (TFFs) are gastrointestinal peptides playing an essential role in the epithelial restitution. Among the three known TFF peptides, TFF1 is characterized by three disulfide bonds producing a compact globular structure and an extended and disordered tail formed by amino- and carboxy-termini. The presence of a cysteine surrounded by several negatively charged residues in this region of the protein, highly conserved in different species, suggests the possible formation of a metal-binding site. Affinity chromatography and mass spectrometric analyses allowed us to demonstrate a selective binding affinity of TFF1 for copper. The binding induces conformational changes in the tertiary structure as demonstrated by circular dichroism experiments, while limited proteolysis revealed an altered access to the cleavage sites in the amino- and carboxy-termini. The results of this study reveal a new property of TFF1 and suggest that copper could influence its biological activities by interfering with the dimerization of the peptide and/or the interaction with mucins or putative TFF receptors.
Keywords: Trefoil factor; TFF1; Copper-binding protein; Copper biosensor; SELDI-TOF;

β-Lactotensin, a neurotensin agonist peptide derived from bovine β-lactoglobulin, enhances memory consolidation in mice by Kousaku Ohinata; Soushi Sonoda; Natsumi Inoue; Rena Yamauchi; Keiji Wada; Masaaki Yoshikawa (1470-1474).
β-Lactotensin (His-Ile-Arg-Leu) is an ileum-contracting tetrapeptide isolated from bovine β-lactoglobulin. We previously reported that a neurotensin agonist β-lactotensin shows antinociceptive effect through neurotensin NT2 receptor. We found that centrally or orally administered β-lactotensin at a dose of 60 nmol/mouse or 300–500 mg/kg, respectively, increased memory consolidation in the step-through-type inhibitory avoidance test in mice. The memory-enhancing activity of β-lactotensin was inhibited by the dopamine D2 receptor antagonist raclopride but not the D1 receptor antagonist SCH23390. Taken together, β-lactotensin might improve memory consolidation through activating the dopamine D2 receptor.

Plant cyclotides: An unusual class of defense compounds by Patrícia B. Pelegrini; Betania F. Quirino; Octávio L. Franco (1475-1481).
Plant cyclotides are unusual peptides with low molecular masses and a three-dimensional structure characterized by the presence of a cyclic fold. Synthetic peptides can adopt this circular conformation, but it is not a common feature for most members of other peptide groups. Cyclotides present a wide range of functions, such as the ability to induce stronger contractions during childbirth and anti-tumor activity. Additionally, some cyclotides present anti-viral, insecticidal or proteinase inhibitory activity. In this paper, we describe the structural and functional characteristics of plant cyclotides, their most conserved features and the development of these peptides for human health and biotechnological applications.
Keywords: Cyclotides; Plant defense; Anti-viral; Insecticide;