Peptide family

Endothelin. The endothelin (ET) peptide family (50) comprises thiee peptides ET-1 (133), ET-2 (134), and ET-3 (135). ET-1, the most abundant, is a 21-amino acid peptide. A 203-amino acid peptide piecuisoi, piepioET, is cleaved after translation by endopeptidases to form a 38-amino acid proET which is converted to active ET by a putative endothelin-converting enzyme (ECE). ET-3 differs from ET-1 and ET-2 by sis amino acids. 

Neuropeptide Y. Neuropeptide Y [82785 5-3] (NPY) (255) is a 36-amiao acid peptide that is a member of a peptide family including peptide YY (PYY) [81858-94-8, 106338-42-5] (256) and pancreatic polypeptide (PPY) [59763-91-6] (257). In the periphery, NPY is present in most sympathetic nerve fibers, particulady around blood vessels and also in noradrenergic perivascular and selected parasympathetic nerves (66). Neurons containing NPY-like immunoreactivity ate abundant in the central nervous system, particulady in limbic stmctures. Coexistence with somatostatin and NADPH-diaphorase, an enzyme associated with NO synthesis, is common in the cortex and striatum. 

Human adrenomedullin is a 52-amino acid peptide belonging to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. It is synthesized mainly in endothelial cells and elicits vasodilation. 

The neuropeptides are peptides acting as neurotransmitters. Some form families such as the tachykinin family with substance P, neurokinin A and neurokinin B, which consist of 11 or 12 amino acids and possess the common carboxy-terminal sequence Phe-X-Gly-Leu-Met-CONH2. Substance P is a transmitter of primary afferent nociceptive neurones. The opioid peptide family is characterized by the C-terminal sequence Tyr-Gly-Gly-Phe-X. Its numerous members are transmitters in many brain neurones. Neuropeptide Y (NPY), with 36 amino acids, is a transmitter (with noradrenaline and ATP) of postganglionic sympathetic neurones. 

Schiller PW, Nguyen TM-D, Berezowska I, Weltrowska G, Schmidt R, Marsden BJ, Wilkes BC, Lemieux C, Chung NN. The TIPP opioid peptide family development of a new class of highly potent 6-receptor antagonists with extraordinary -selectivity. In Yanaihara N, ed. Peptide Chemistry 1992 (Proceedings of the 2nd Japanese Symposium on Peptide Chemistry. Leiden, The Netherlands Escom Science Publishers, 1993 337-340. 

In addition to its pump function, the heart is also a secretory organ. Cardiac cells produce two small peptides, the natriuretic factors, which oppose the vasoconstrictive actions of noradrenaline (norepinephrine) from the sympathetic nervous system and of the peptide angiotensin II. By causing vasodilation and natriuresis (increased excretion of sodium in the urine), atrial natriuretic peptide (ANP) secreted from the atria and B-type natriuretic peptide (BNP) secreted by both atria and probably more significantly, from the ventricles, reduce blood pressure. The stimulus to secretion of natriuretic peptides is wall stretch of the chambers of the heart, indicating volume and pressure overload of the vascular system. A third member of the natriuretic peptide family, CNP, is secreted by endothelial cells. 

In addition to the cathelicidins and defensins, humans also utilize a variety of other host defense peptides. Examples of these include the anionic dermcidins, found in human sweat and possessing potent antimicrobial activity in a broad range of pH and salt concentrations, and the histatins, a histidine-rich host defense peptide family found in humans and higher primate species. The histatins are normally found in saliva and utilize an alternative mechanism to bacterial membrane lysis for their antimicrobial activity. ... 

The peptides discussed so far are defined by a common genetic pattern or architectural feature, such as their sequence or disulfide bond pattern. In this section we discuss peptides that share a common mode of action but may arise from different peptide families. Proteinase inhibitors (Pis) come in an astounding range of sizes, from the smallest gene-encoded cyclic peptide known to date, sunflower trypsin inhibitor 1 (SFTI-1), ° a 14-residue cyclic peptide with a single disulfide bond, to squash inhibitors that are approximately 30 residues in size and feature the cystine knot motif, to 53-residue Pis found in Nicotiana... 

Some of the peptide families here have been successfully expressed in standard laboratory bacterial or yeast expression systems. This approach allows the production of larger amounts of peptides not amenable to chemical synthesis and opens the potential of large-scale production for biotechnological uses, for example, as plant protection agent applied externally. 

Severini C, Improta G, Falconieri-Erspamer G, Salvador S, Erspamer V (2002) The tachykinin peptide family. Pharmacol Rev 54 285-322... 

Dautzenberg FM, Hauger RL (2002) The CRF peptide family and their receptors yet more partners discovered. Trends Pharmacol Sci 23 71-77 De Araujo JE, Silva RCB, Huston JP, Brandao ML (1999) Anxiogenic effects of substance P and its 7-11 C terminal, but not the 1-7 N terminal, injected into the dorsal periaqueductal gray. Peptides 20 1437-1443... 

Natriuretic peptides are naturally occurring substances in the body that oppose the activity of the renin-angiotensin system. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). All three natriuretic peptides are synthesized from cleavage of a larger precursor polypeptide. In the ventricles and brain, the synthesis of BNP predominates ANP is synthesized by cardiac myocytes predominately in the atria and CNP is synthesized in the brain, blood vessels, and kidney. 

Dautzenberg FM and Hauger RE. The CRF peptide family and their receptors yet more partners discovered. Trends Pharmacol Sci 2002 23 71-78. 

Hegde VR, Puar MS, Dai P, Patel M, Gullo VP, Chan T-M, Silver J, Pramanik BN, Jenh C-H (2003) Condensed Aromatic Peptide Family of Microbial Metabolites, Inhibitors of CD28-CD80 Interactions. Bioorg Med Chem Lett 13 573... 

There are dozens of presynaptic receptors for endogenous peptides. This review will focus on receptors for four peptides or peptide families the opioid peptides, neuropeptide Y and related peptides, adrenocorticotropic hormone (corticotropin, ACTH), and the orexins. This choice is representative, since part of the receptors inhibit and part of them facilitate transmitter release moreover, the receptors under consideration are coupled to the major G proteins, namely Gl/(), Gs and Gq (Table 1). 

Table 1 Synopsis of Receptors Activated by the Four Peptide Families...

Fig. 1 First description of the four peptides (or peptide families) and their respective presynaptic receptors. The papers are (from left to right) Trendelenburg (1917) Hughes et al. (1975) Tatemoto et al. (1982) Allen et al. (1982) Collip et al. (1933) Gothert (1981) de Lecea et al. (1998) van den Pol et al. (1998).

Sudoh T, Minamino N, Kangawa K, Matsuo H (1990) C-type natriuretic peptide (CNP) a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun 168 863-70... 

Schoofs L., Holman G. M., Hayes T. K., Nachman R. J. and Loof A. D. (1990a). Isolation, identification and synthesis of locustamyotropin II, an additional neuropeptide of Locusta migratoria member of the cephalomyotropic peptide family. Insect Biochem. 20, 479-484. 

Otvos, L., Jr. (2002) The short proline-rich antibacterial peptide family. Cell Mol. Life Sci. 59, 1138-1150. 

The first peptide family of amphibian opiates was discovered in 1981 and named dermorphins [2,3], Until the discovery of mammalian endomor-phins by Zadina et al. [4], these peptides represented the most potent and selective mu opiate receptor agonists identified in living organisms. Nine years later, deltorphins were discovered in the amphibian skin. These peptides are still the most potent and selective delta opiate agonists available today [5]. 

Additional modifications of POMC peptide family There are extensive additional modifications of these peptides. Much of the N-terminal peptides of POMC as well as ACTH are glycosylated in the anterior pituitary. a-MSH is found predominantly in an N-acetylated and carboxy terminal amidated form. /3-Endorphin is rapidly acetylated in the intermediate lobe and made less active. In the hypothalamus /3-endorphin is not acetylated and is presumably active. /8-Endorphin is also trimmed in the intermediate lobe at the C-terminal end to form a- and y-endorphin. The large N-terminal fragment is also extensively cleaved but not much is known about this fragment. 

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