Peptides endogenous

The endogenous peptide dynorphin and its C-terminally degraded fragments dynorphin A 3 and dynorphin A2 c, are somewhat K-selective... 

Several methods are being studied to enhance the stabiUty of peptide mimics and improve their stereochemical similarity to the endogenous peptides. For example, the tetrapeptide Cys—Val—Phe—Met, a potent inhibitor of Ras famesyltransferase, is proposed to exist in a turned conformation, which mimics the endogenous peptide during enzyme binding. This conformation is successhiUy mimicked by 3-amino-l-carboxymethyl-5-phenyl-benzodiazepin-2-onederivatives (198) (142). 

Jardetzky, T.5., Wiley, D.C. Crystallographic analysis of endogenous peptides associated with HLA-DRl suggests a common, polyproline Il-like conformation for hound peptides. Proc. Natl. Acad. Sci. USA 93 734-728, 1996. 

Murthy, V.L., 5tern, L.J. The class II MHC protein HLA-Drl in complex with an endogenous peptide implications for the structural basis of the specificity of peptide binding. Structure 5 1385-1396, 1997. 

Tatemoto K, Hosoya M, Habata Y et al (1998) Isolation and characterization of a novel endogenous peptide ligand for the human API receptor. Biochem Biophys Res Commun 251 471-476... 

Endogenous opioid peptides are the wide variety of endogenous peptides isolated since 1975 which are the natural ligands for the opioid receptors. The peptides... 

INTERACTION OF OPIOID RECEPTORS WITH ENDOGENOUS PEPTIDE LIGANDS... 

The mu, kappa, and delta opioid receptors have been found to interact with endogenous peptide ligands that share certain pharmacologic properties with opioid drugs. These peptide ligands are derived from at least three different prohormones located in both... 

Somatostatin. Somatostatin is an endogenous peptide hormone involved in e.g. the control of the release of Somatomedin, Insulin and Pancreatin. Due to its biological role, Somatostatin has a very low biological stability. The half-life in the rabbit after intravenous administration has been determined to approximately 90 seconds in this investigation. After sc or im administration, the apparent half-life is somewhat longer, close to 10 minutes, probably due to the absorption of the peptide from the injection site into the systemic circulation. 

Rousselle J-C, Massot O, Delepierre M, Zifa E, Fillion G. Isolation and characterization of an endogenous peptide from rat brain interacting specifically with the serotonergic IB receptor subtypes. J Biol Chem 1996 271 551-557. 

Ouellette, A.J. and Selsted, M.E. (1996) Paneth cell defensins endogenous peptide components of intestinal host defense. FASEB Journal 10, 1280-1289. 

Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide secreted by the ventricular myocardium in response to volume overload. Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation increases in cardiac output natriuresis and diuresis and decreased cardiac filling pressures, sympathetic nervous system activity, and renin-angiotensin-aldosterone system activity. 

SwePep (http //www.swepep.com/), endogenous peptide database to aid their identification by MS. 

Chapter 3 describes the 1-benzazepine family, particularly in relation to their use in the treatment of certain forms of hypertension resulting from inhibition of angiotensin-converting enzymes. In Chapter 4, regulation of the role of mast cells in the control of the microenvironment, and tissue growth and repair by many endogenous peptides is reviewed. 

Endogenous peptides, protein substances and their analogs are generally not required to be evaluated for carcinogenicity. There are three conditions which call the need into question ... 

Derivatization to protect endogenous peptides or create prodrugs thereof. 

Numerous studies have been published on the in vivo metabolism of peptides. However, these studies are concerned mainly with assessment of pharmacokinetic parameters such as half-life and clearance. Only seldom is the in vivo biotransformation of peptides that contain only common amino acids investigated in any detail, due to the difficulty of monitoring products of proteolysis that are identical to endogenous peptides and amino acids. More importantly, such studies fail to yield mechanistic and biochemical insights. For this reason, we begin here with a discussion of the metabolism of just a few peptides in some selected tissues, namely portals of entry (mouth, gastro-intestinal tract, nose, and skin), plasma, organs of elimination (liver, kidney), and pharmacodynamic sites (brain and cerebrospinal fluid). These examples serve as introduction for the presentation in Sect. 6.4.2 of the involvement of individual peptidases in peptide metabolism. 

Even cursory inspection of peptides collected in Table 2.1 provides compelling evidence that the diversity of endogenous peptides is comprised of a much broader set of components than traditional hormones, neuromodulators and antibiotics. In spite of the availability of scattered data on the activity of selected pool components the principal question on the biological role of peptide pools remains unanswered does the bulk of pool peptides represent transient products of protein substrate destmction on their way to reusable amino acid building blocks Or do these peptides perform a useful regulatory function The answer to these questions requires systematic study of a large number of samples in adequate biological test systems. 

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