118460-00-7Relevant articles and documents
Unconventional Secondary Structure Mimics: Ladder-Rungs
Arancillo, Maritess,Burgess, Kevin,Lin, Chen-Ming,Whisenant, Jonathan
, p. 9398 - 9402 (2020)
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.
Diversity-oriented synthesis of macrocyclic peptidomimetics
Isidro-Llobet, Albert,Murillo, Tiffanie,Bello, Paula,Cilibrizzi, Agostino,Hodgkinson, James T.,Galloway, Warren R. J. D.,Bender, Andreas,Welch, Martin,Spring, David R.
scheme or table, p. 6793 - 6798 (2012/03/26)
Structurally diverse libraries of novel small molecules represent important sources of biologically active agents. In this paper we report the development of a diversity-oriented synthesis strategy for the generation of diverse small molecules based around a common macrocyclic peptidomimetic framework, containing structural motifs present in many naturally occurring bioactive compounds. Macrocyclic peptidomimetics are largely underrepresented in current small-molecule screening collections owing primarily to synthetic intractability; thus novel molecules based around these structures represent targets of significant interest, both from a biological and a synthetic perspective. In a proof-of-concept study, the synthesis of a library of 14 such compounds was achieved. Analysis of chemical space coverage confirmed that the compound structures indeed occupy underrepresented areas of chemistry in screening collections. Crucial to the success of this approach was the development of novel methodologies for the macrocyclic ring closure of chiral α-azido acids and for the synthesis of diketopiperazines using solid-supported N methylmorpholine. Owing to their robust and flexible natures, it is envisaged that both new methodologies will prove to be valuable in a wider synthetic context.
Efficient method to prepare hydroxyethylamine-based aspartyl protease inhibitors with diverse P1 side chains
Chino, Masao,Wakao, Masahiro,Ellman, Jonathan A
, p. 6305 - 6310 (2007/10/03)
An efficient procedure for the solid-phase synthesis of hydroxyethylamine-based aspartyl protease inhibitors is described. The 1,2-bromo alcohol 4 is the key intermediate and is prepared in four-steps in good overall yield from commercial available amino acids.
