High impact information on diprotin A

• Conversion to GRH(3-44)-NH2 was blocked by diprotin A, a DPP type IV (DPP IV) competitive inhibitor [1].
• Treatment of transduced bone marrow cells with Diprotin A permitted long-term expression of a retrovirally encoded MHC class I gene on multiple hematopoietic cell lineages after transplantation of a suboptimal number of transduced cells [2].
• These products were significantly reduced when the specific DPP IV inhibitor diprotin A was included in the incubation mixture and were absent when serum from DPP IV-deficient rats was used [3].
• Enalaprilat (an inhibitor of kininase II) blocked the formation of BK1-7 and BK1-5 and increased the recovery of BK4-9. beta-Mercapto-ethanol, which inhibits aminopeptidase P, and diprotin A, a specific inhibitor of dipeptidylaminopeptidase IV, both reduced the formation of BK4-9 [4].
• One of them cleaves the prolyl bond in the synthetic dipeptide nitroanilide Gly-Pro-pNA (Km 0.95 mM and Vmax 8 nmol/h at pH 7.4 and 37 degrees C) and is specifically inhibited by phenylmethane sulfonyl fluoride, diprotin A, Gly-Pro-Ala and Gly-Pro-Gly-Gly [5].

Biological context of diprotin A

• NEP-24.11 was inhibited by phosphoramidon (IC50 = 80 nM), thiorphan and ZINCOV, DAP IV by diprotin A (IC50 = 8 microM), and APN by amastatin (IC50 = 50 nM) and bestatin (IC50 = 100 microM) [6].
• Pre-treatment of guinea-pigs with both phosphoramidon and diprotin A resulted in a small non-significant increase in the cough response (2.8+/-0.9 vs. 1.1+/-0.6; P>0.05) but significantly enhanced substance P-induced bronchoconstriction (P<0.05) [7].
• In order to elucidate the binding mode and substrate specificity, we determined the crystal structure complex of hDPPIV and diprotin A (IIe-Pro-IIe), a slowly hydrolyzed substrate of hDPPIV, at 2.2 A resolution [8].
• Furthermore, SDF-1/CXCL12 induced chemotaxis of ESCs, and chemotaxis could be enhanced by diprotin A inhibition of CD26/dipeptidylpeptidase IV [9].
• The Glu motif provides recognition and a binding site for the N terminus of the substrates, as revealed by the complex structure with diprotin A, a substrate with low turnover that is trapped in the tetrahedral intermediate of the reaction in the crystal [10].

Anatomical context of diprotin A

• Here, we demonstrate that treatment of retrovirally transduced mouse bone marrow cells with the tri-peptide Diprotin A (Ile-Pro-Ile), a specific inhibitor of CD26, significantly enhances engraftment of retrovirally transduced HSCs [2].
• In vitro permeation studies revealed that the permeability coefficient of ENI across porcine buccal epithelium was 5.67+/-4.74x10(-7) cm/s. The enzymatic degradation of ENI was found not to be rate limiting to the drug's permeation across buccal epithelium, as diprotin-A did not increase the permeation of ENI [11].
• The dipeptidyl aminopeptidase IV (DP IV) inhibitor Diprotin A produces a full, dose-dependent, short-lasting and naloxone-reversible analgesia in the rat tail-flick test when given intracerebroventricularly, with an ED50 of 295 nmol/rat but it has no direct opioid agonist activity in the longitudinal muscle strip of guinea-pig ileum bioassay [12].
• In this study, we determined cell growth, insulin content, insulin accumulation and insulin secretory function of a insulin-secreting cell line cultured for 3 days with either GLP-1, GLP-1 plus the DPP IV inhibitor diprotin A (DPA) or stable N-acetyl-GLP-1 [13].

Associations of diprotin A with other chemical compounds

• Among various inhibitors tested, diprotin A and phenylmethylsulfonyl fluoride inhibited the enzymatic activity, suggesting that the enzyme induced by IL-1alpha was DPPIV [14].
• One activity removing dipeptides from the NH2-terminal end of Gly-Pro-pNA was specifically inhibited by di-isopropyl-fluorophosphate (DFP), phenylmethanesulphony fluoride (PMSF), and diprotin A, and thus was identified as dipeptidyl peptidase IV (DPP IV) [15].
• The effects of endomorphins and diprotin A on striatal dopamine release induced by electrical stimulation-An in vitro superfusion study in rats [16].
• When combined in HIV-1-infected cell cultures, IlePyr and Diprotin A (DP-A), another CD26/DPP IV inhibitor, abrogated the antiviral activity of GPG-NH2 but not of G-NH2 [17].
• They were abolished by RP67580, a NK1 receptor antagonist, and increased by phosphoramidon or diprotin A [18].

Gene context of diprotin A

• In this paper, we discuss the molecular interaction mechanism of diprotin A with hDPPIV based on the X-ray crystal structure [8].
• The DPIV-like activity was specifically inhibited by both Diprotin A and B, non-competitively, generating a K(i) of 1.4 x 10(-4) M for both inhibitors [19].
• The recombinant DPP IV showed a high affinity for the synthetic peptide glycine-proline-p-nitroanilide and was strongly inhibited by Hg2+ and diprotin A [20].
• 5. Diprotin A (Ile-Pro-Ile) was an efficient competitive inhibitor of the cockroach DPP, whereas other known DPP inhibitors were found to be less potent [21].
• The formation of GIP(3-42) was almost completely abolished by inhibition of plasma DPP IV with diprotin A [22].

Analytical, diagnostic and therapeutic context of diprotin A

• Expression of the allogeneic MHC class I antigen on bone marrow-derived cells following transplantation of Diprotin A-treated cells was sufficient to induce transplantation tolerance [2].
• An in vitro superfusion system was utilized to investigate the actions of EM1, EM2 and specific DPPIV inhibitor diprotin A on the striatal release of dopamine (DA) induced by electrical stimulation in rats [16].
• Diprotin A, an inhibitor of dipeptidyl aminopeptidase IV(EC 3.4.14.5) produces naloxone-reversible analgesia in rats [12].

References