6234-26-0Relevant articles and documents
Rapid and controllable hydrogen/deuterium exchange on aromatic rings of α-amino acids and peptides
Murai, Yuta,Wang, Lei,Masuda, Katsuyoshi,Sakihama, Yasuko,Hashidoko, Yasuyuki,Hatanaka, Yasumaru,Hashimoto, Makoto
supporting information, p. 5111 - 5116 (2013/11/06)
Novel hydrogen/deuterium exchange for aromatic α-amino acids and their corresponding peptides were performed through the use of deuterated trifluoromethanesulfonic acid (TfOD). Detailed analysis of the exchange revealed that equal hydrogen/deuterium excha
Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: A strategy for the design of peptidase inhibitors
Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Law, James K.,Marabout, Benoit,Luthra, Pratibha Mehta,Moore, Andrew N. J.,Peschard, Olivier,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
, p. 664 - 674 (2007/10/03)
The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 μM) and Ala-Pro-Ala-OH (K(i) = 3 μM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 μM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 μM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.
SYNTHESIS, PROPERTIES, AND REACTIONS OF α- AND β-D-GLUCOPYRANOSYL ESTERS OF SOME TRIPEPTIDES
Valentekovic, Stefica,Keglevic, Dina
, p. 31 - 44 (2007/10/02)
The 2,3,4,6-tetra-O-benzyl-1-O-(N-benzyloxycarbonyltripeptidyl)-D-glucopyranoses 1, 8, and 13 were synthesised from 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose and the active esters of the appropriate N-protected tripeptides (Gly-Gly-Gly-, L-Phe-Gly-Gly-, and Gly-Gly-L-Phe-) in the presence of imidazole; the anomeric mixtures were resolved and the α and β anomers characterised.The β anomer of 13, containing the L and D enantiomers (ratio ca. 3:1) of Gly-Gly-Phe- as the aglycon, could be resolved by column chromatography into the pure isomeric forms.Catalytic hydrogenolysis of the β anomers, in the presence and absence of a strong acid, yielded the free 1-esters 2β, 9β, and 14β, which were characterised as the mono-oxalate or trifluoroacetate salts and as free bases.Similarly, the α anomers afforded 2α, 9α, and 14α, whereas omission of the strong acid led to accompanying 1 --> 2 acyl migration, to give the 2-O-acyl derivatives.All of the compounds prepared were converted into the N-acetyl and/or peracetylated derivatives.The 1-esters 2β and 9β, both in the charged and uncharged form, and the trifluoroacetate salt of 14β, are susceptible to cleavage by β-D-glucosidase; the enzyme had no effect on the uncharged form of 14β.This difference between 14β and its salt is discussed in conformational terms.
