67943-19-5Relevant academic research and scientific papers
The implications of (2S,4S)-hydroxyproline 4-O-glycosylation for prolyl amide isomerization
Owens, Neil W.,Lee, Adrian,Marat, Kirk,Schweizer, Frank
experimental part, p. 10649 - 10657 (2010/05/19)
The conformations of peptides and proteins are often influenced by glycans O-linked to serine (Ser) or threonine (Thr). (25,4R)-4-Hydroxyproline (Hyp), together with L-proline (Pro), are interesting targets for O-glycosylation because they have a unique influence on peptide and protein conformation. In previous work we found that glycosylation of Hyp does not affect the N-terminal amide transieis ratios (Ktrans/cis) or the rates of amide isomerization in model amides. The stereoisomer of Hyp-(25,4S)-4-hydroxyproline (hyp)-is rarely found in nature, and has a different influence both on the conformation of the pyrrolidine ring and on Ktrans/cis Glycans attached to hyp would be expected to be projected from the opposite face of the prolyl side chain relative to Hyp; the impact this would have on K trans/cis was unknown. Measurements of 3J coupling constants indicate that the glycan has little impact on the Cy-endo conformation produced by hyp. As a result, it was found that the D-galactose residue extending from a Cy-endo pucker affects both K trans/cis and the rate of isomerization, which is not found to occur when it is projected from a Cy-exo pucker; this reflects the different environments delineated by the proline side chain. The enthalpic contributions to the stabilization of the trans amide isomer may be due to disruption of intramolecular interactions present in hyp; the change in enthalpy is balanced by a decrease in entropy incurred upon glycosylation. Because the different stereoisomers-Hyp and hyp-project the O-linked carbohydrates in opposite spatial orientations, these glycosylated amino acids may be useful for understanding of how the projection of a glycan from the peptide or protein backbone exerts its influence.
Design, synthesis and preliminary evaluation of novel pyrrolidine derivatives as matrix metalloproteinase inhibitors
Cheng, Xian-Chao,Wang, Qiang,Fang, Hao,Tang, Wei,Xu, Wen-Fang
, p. 2130 - 2139 (2008/12/22)
A series of novel pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The hydroxamates 8a-c were equally or more potent MMP-2 inhibitors than the positive control LY52. The binding mode of the most potent compound 8a with MMP-2 was proposed. Structure-activity relationships were also briefly discussed.
Two prolines with a difference: contrasting stereoelectronic effects of 4R/S-aminoproline on triplex stability in collagen peptides [pro(X)-pro(Y)-Gly]n.
Umashankara,Babu, I Ramesh,Ganesh, Krishna N
, p. 2606 - 2607 (2007/10/03)
4R/S-Aminoprolines when present in the X-position of collagen peptide [pro(X)-pro(Y)-Gly]n exhibit pH- and stereochemistry-dependent effects on triplex stability.
Studies of N-Terminal Templates for α-Helix Formation. Synthesis and Conformational Analysis of (2S,5S,8S,11S)-1-Acetyl-1,4-diaza-3-keto-5-carboxy-10-thiatricyclo4,8>tridecane (Ac-Hel1-OH)
Kemp, D. S.,Curran, Timothy P.,Davis, William M.,Boyd, James G.,Muendel, Christopher
, p. 6672 - 6682 (2007/10/02)
A convergent synthesis of the title compound, a conformationally restricted analogue of acetyl-L-prolyl-L-proline, from 1-acetyl-2(S)-carboxy-4(S)-mercaptopyrrolidine and trans-1-(tert-butoxycarbonyl)-2(S)-(methoxycarbonyl)-5(S)-pyrrolidine (Ac-Hel1-OH) is reported, along with a synthesis of (2S,8S,11S)-1-acetyl-1,4-diaza-3-keto-10-thiatricyclo4,8>tridecane.In the crystal and in CDCl3 solution the conformation of Ac-Hel1-OH is shown to approximate a staggered orientation at the 8,9-CC bond and an s-cis orientation at the acetyl amide bond.In DMF, DMSO, MeCN, and D2O significant amounts of the s-trans conformer are also present.
