146803-47-6Relevant articles and documents
Unconventional Secondary Structure Mimics: Ladder-Rungs
Arancillo, Maritess,Burgess, Kevin,Lin, Chen-Ming,Whisenant, Jonathan
, p. 9398 - 9402 (2020/05/05)
Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well-defined patterns. Bioinformatics studies to match side-chain orientations of a novel hydantoin triazole chemotype (1) to protein-protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein-protein interaction uPA?uPAR. Consequently, chemotype 1 was made with appropriate side-chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing.
Incorporation of a bioactive reverse-turn heterocycle into a peptide template using solid-phase synthesis to probe melanocortin receptor selectivity and ligand conformations by 2D 1H NMR
Singh, Anamika,Wilczynski, Andrzej,Holder, Jerry R.,Witek, Rachel M.,Dirain, Marvin L.,Xiang, Zhimin,Edison, Arthur S.,Haskell-Luevano, Carrie
, p. 1379 - 1390 (2011/05/12)
By use of a solid-phase synthetic approach, a bioactive reverse turn heterocycle was incorporated into a cyclic peptide template to probe melanocortin receptor potency and ligand structural conformations. The five melanocortin receptor isoforms (MC1R-MC5R) are G-protein-coupled receptors (GPCRs) that are regulated by endogenous agonists and antagonists. This pathway is involved in pigmentation, weight, and energy homeostasis. Herein, we report novel analogues of the chimeric AGRP-melanocortin peptide template integrated with a small molecule moiety to probe the structural and functional consequences of the core His-Phe-Arg-Trp peptide domain using a reverse-turn heterocycle. A series of six compounds are reported that result in inactive to full agonists with nanomolar potency. Biophysical structural analysis [2D 1H NMR and computer-assisted molecular modeling (CAMM)] were performed on selected analogues, resulting in the identification that these peptide-small molecule hybrids possessed increased flexibility and fewer discrete conformational families compared to the reference peptide and result in a novel template for further structure-function studies.
DMSO-aided o-iodoxybenzoic acid (IBX) oxidation of Fmoc-protected amino alcohols
Chen, Jack J.,Aduda, Vince
, p. 3493 - 3499 (2008/03/13)
A fast and highly convenient procedure for the formation of Fmoc-protected amino aldehydes from the corresponding alcohols using 1.1 equiv. of IBX in the presence of dimethylsulfoxide (DMSO) is discussed. This procedure leads to the clean synthesis of Fmo
