Dipeptidyl

Dipeptidyl aminopeptidase (from rat brain) [9031-94-1] [EC 3.4.11.10]. Purified about 2000-fold by column chromatography on CM-cellulose, hydroxylapatite and Gly-Pro AH-Sepharose. [Imai et al. J Biochem (Tokyo)93 431 1983.]... 

The incretin effect is reduced in type 2 diabetes, and this is attributed, at least in part, to reduced secretion of GLP-1. The biological actions of GLP-1 remain essentially intact in type 2 diabetes, but administration of extra GLP-1 is not a practical therapeutic option because the peptide is degraded rapidly if A < 2 min) by the enzyme dipeptidyl peptidase IV (DPP-4). DPP-4 cleaves the N-terminal dipeptide from many of the peptides that have either an alanine or a proline residue penultimate to the N-terminus (Fig. 6). 

DPP-1V inhibitors Inhibition of the dipeptidyl peptidase IV (by sitagliptin or vildagliptin) prolongs the duration of action of endogenous GLP-1 and thereby... 

Importantly, both incretins when secreted by the intestine are rapidly degraded by the dipeptidyl peptidase IV (DPPFV), which removed the two amino-terminus histidine-alanine residues, thereby, inactivating the incretins. This enzyme is present at the surface of the epithelial intestinal cells and capillaries in the vicinity of the K and L cells secreting GIP and GLP-1, respectively. It is also present in the... 

CA C1 C01.070 Dipeptidyl-peptidase I Potential therapeutic target for treatment of sepsis... 

There are several different types of exopeptidases aminopeptidases, carboxypeptidases, dipeptidyl-peptidases, tripeptidy 1-peptidases, peptidyl-... 

Alternate ways to interfere with the orexin system may be via inhibition of dipeptidyl peptidases or proteolysis-resistant peptide analogs as shown for other peptides. This could prolong and boost orexinergic signaling. OX-A but not OX-B can enters the brain by simple diffusion via the blood-brain barrier. Abundance of orexins and their receptors in the olfactory bulb and throughout all parts of the central olfactory system may offer transnasal routes for drug application. 

It has been shown that the stereochemistry of starting dipeptidyl chloromethyl ketones does not influence the cycHzation reaction, but the chlorine... 

An efficient biocatalytic method for the production of amides in multigrara scale has been developed for the synthesis of a pyrrole-amide, which is an intermediate for the synthesis of the dipeptidyl peptidase IV that regulates plasma levels of the insulinotropic proglucagon. CALB catalyzes the ammonolysis of the ester with ammonium carbamate as source of ammonia (Scheme 7.8) [22]. The use of ascarite and calcium chloride as adsorbents for carbon dioxide and ethanol by-products. 

The exchange of the chiral phenylethyl amine against an optically active amino acid fragment 269 allowed the synthesis of conformationally restrained dipeptidyl lactams 271 and 272 including the so called Freidinger lactams as... 

McAlexander L, Sinha T, et al Dipeptidyl peptidase IV deficiency increases susceptibifity to angiotensinconverting enzyme inhibitor-induced peritracheal edema. J Allergy Chn Immunol 2007 120 403-408. 

Ajami K, Pitman MR, Wilson CH et al (2008) Stromal cell-derived factors lalpha and Ibeta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8. FEBS Lett 582 819-825 Albright AV, Shieh JT, O Connor Ml et al (2000) Characterization of cultured microglia that can be infected by HIV-1. J Neurovirol 6(Suppl 1) S53-S60 Allen SJ, Crown SE, Handel TM (2007) Chemokine receptor structure, interactions, and antagonism. Annu Rev Immunol 25 787-820... 

Hosono O, HommaT, Kobayashi H et al (1999) Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals. Qin Immunol 91 283-295... 

Another interesting target for this type of inhibitors is the dipeptidyl peptidase IV (DPP IV). This exodipeptidase, which can cleave peptides behind a proline residue is important in type 2 diabetes as it truncates the glucagon-like peptide 1. Taking into account the P2-Pi( Pro)-P,1 cleavage and the requirement for a free terminal amine, the synthesis of a suicide inhibitor was planned. It looked as if the the e-amino group of a P2 lysine residue could be cyclized because of the relative little importance of the nature of the P2 residue on the rate of enzymatic hydrolysis of known synthetic substrates. Therefore, anew series of cyclopeptides 11 was synthesized (Fig. 11.8). 

Nguyen, C. Blanco, J. Mazaleyrat, J.-P. Krust, B. Callebaut, C. Jacotot, E. Hovanessian, A. G. Wakselman, M. Specific and irreversible cyclopeptide inhibitor of dipeptidyl peptidase IV activity of the T-cell activation antigen CD26. J. Med. Chem. 1998, 41, 2100-2110. 

Lambeir AM, Proost P, Durinx C, et al. Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family. J Biol Chem 2001 276(32) 29839-29845. 

---