Dipeptidylpeptidase

Dipeptidylpeptidase IV (also known as CD26) cleaves neuropeptide Y, and peptide YY to generate their subtype-selective fragments NPY3 36 and PYY3 36. 

NPY is primarily (but not exclusively) synthesised and released by neurons, which in the peripheral nervous system are predominantly sympathetic neurons [1]. In most cases, NPY acts as a co-transmitter that is preferentially released upon high frequency nerve stimulation. NPY can be metabolised by the enzyme dipeptidylpeptidase IV (also known as CD26) to generate the biologically active fragment NPY3 36. 

L-Dihydroxyphenylalanine 4-Dihydroxyphenylethylamine Dimeric Transcription Factors Dioxins Dipeptidase Dipeptidylpeptidase Dipeptidylpeptidase IV Direct Thrombin Inhibitors Discharge of Neurons... 

A number of allergens from both honey bee and vespid venoms have been cloned and expressed by either Escherichia coli or baculovirus-infected insect cells (table 1) phospholipase Aj [20], hyaluronidase [21], acid phosphatase [13] and Api m6 [14] from honey bee venom, as well as antigen 5 [22], phospholipase A and hyaluronidase [23] from vespid venom, and dipeptidylpeptidases from both bee and Vespula venoms [15, 16]. Their reactivity with human-specific IgE antibodies to the respective allergens has been documented [11-16, 22, 23] and their specificity is superior... 

Christopherson KW 2nd, Hangoc G, Broxmeyer HE. Cell surface peptidase CD26/ dipeptidylpeptidase IV regulates CXCL12/stromal cell-derived factor-1 alpha-mediated chemotaxis of human cord blood CD34+ progenitor cells. J Immunol 2002 169(12) 7000-7008. 

L. A. Frohman, T. R. Downs, E. P. Heimer, A. M. Febx, Dipeptidylpeptidase IV and Trypsin-Like Enzymatic Degradation of Human Growth Hormone-Releasing Hormone in Plasma , J. Clin. Invest. 1989, 83, 1533-1540. 

Sitagliptin is a dipeptidylpeptidase-4 inhibitor that increases insulin secretion and lowers glucagon secretion. Sitagliptin is available for oral administration. It is indicated in patients with type 2 diabetes mellitus in combination with either metformin (biguanide) or a sulphonylurea or a thiazolidinedione. 

Sitagliptin is a selective dipeptidylpeptidase 4 (DPP-4) inhibitor which increases the active form of GLP-1 (glucagon-like-peptide-1) and GIP (glucose-dependent insulinotropic peptide). This enzyme-inhibiting drug is to be used either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. Adverse effects were as common with sitagliptin (whether used alone or with metformin or pioglitazone) as they were with placebo, except for nausea and common cold-like symptoms. 

Several fluorine-containing drugs are currently in development for the treatment of diabetes. These are peroxisome proliferator-activated nuclear receptor (PPAR) agonists, aldose reductase, and dipeptidylpeptidase IV (DPP-IV) inhibitors. 

The incretin hormone glucagon-like peptide-1 (GLP-1) plays a crucial role in the regulation of insulin by acting on the pancreas to potentiate glucose-induced insulin secretion. GLP-1 is rapidly cleaved by serine protease dipeptidylpeptidase IV. The inhibitors of DDP-IV are new drugs for the oral treatment of type 2 diabetes. 

There are at least three peptidases in the brush border of the small intestine Aminopeptidase A, which has an affinity for peptide-bound acid amino acids (11), aminopeptidase N, which has a broad specificity (12), and dipeptidylpeptidase IV, which releases dipeptides from the N-terminal end of peptides with a preference for X-PRO terminals (13). In Table III are shown the effect of a low concentration ofThe LMW fraction on the activity of these enzymes in extracts of hog intestine. Aminopeptidase N was found to be strongly inhibited by 0.25 mg/ml of the fraction. Aminopeptidase A and dipeptidylpeptidase IV were not inhibited. 

Little is known about the in vivo regulation of MDC function. In vitro studies have shown that MDC is a substrate for the dipeptidylpeptidase CD26, which removes the first two or four amino acids from the mature form of MDC (Struyf et al, 1999). MDC which is modified in this fashion will no longer interact with CCR4 and is no longer chemotactic for T lymphocytes (Proost et al, 1999). However these truncated forms of MDC retain their ability to stimulate monocyte chemotaxis and to inhibit HIV replication in vitro, suggesting that additional receptors for MDC may exist (Proost et al, 1999 struyf et al, 1999). 

Dipeptidylpeptidase IV (EC 3.4.11.5 postproline dipeptidyl aminopeptidase CD26) is a serine protease located in the plasma membrane. Notable neuropeptide substrates include substance P. neuropeptide Y, peptide YY and enterostatin. Inhibitors include diprotin A (lle-Pro-lle) and diprotin B (Val-Pro-Leu)... 

Diprosone betamethasone. diprOtin A is a tripeptide that is an ENZYME INHIBITOR with selectivity as an aminopeptidase inhibitor active against dipeptidylpeptidase IV (EC 3.4.11). It can be used as a pharmacological tool in experimental analytical studies, dipyridamole [ban, inn, usan] (Persantin ) is a pyrimidine derivative, a coronary VASODILATOR, a (class la) ANTIARRHYTHMIC, an adenosine UPTAKE INHIBITOR causing indirect adenosine receptor activation, and enhances effects of anticoagulants and is a platelet AGGREGATION INHIBITOR. 

Peptidases. Others members of the serine protease family, cleave oligopeptides and do not necessarily act on proteins. These include two peptidases of particular interest (dipeptidylpeptidase IV and proline endopeptidase). See also AMINOPEPTIDASE INHIBITORS CARBOXYPEPTIDASE INHIBITORS ... 

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