[reaction: see text] We introduce all stereoisomers of a bis-amino acid building block derived from trans-4-hydroxy-L-proline. This small library of monomers allows arbitrary stereochemical configuration at any chiral center within our spiro-ladder oligomers. Three tetramer oligomers containing several combinations of the monomers 1-4 were synthesized; we explored the effect of monomer sequence on scaffold conformation by NMR.
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http://dx.doi.org/10.1021/ol060902q | DOI Listing |
Angew Chem Int Ed Engl
July 2023
Department of Chemistry, Temple University, 1901N. 13th St., Philadelphia, PA-19122, USA.
Here, we report a new class of peptidomimetic macrocycles with well-defined three-dimensional structures and low conformational flexibility. They are assembled from fused-ring spiro-ladder oligomers (spiroligomers) by modular solid-phase synthesis. Two-dimensional nuclear magnetic resonance confirms their shape persistency.
View Article and Find Full Text PDFPLoS One
April 2013
Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America.
We demonstrate functionalized spiroligomers that mimic the HDM2-bound conformation of the p53 activation domain. Spiroligomers are stereochemically defined, functionalized, spirocyclic monomers coupled through pairs of amide bonds to create spiro-ladder oligomers. Two series of spiroligomers were synthesized, one of structural analogs and one of stereochemical analogs, from which we identified compound 1, that binds HDM2 with a Kd value of 400 nM.
View Article and Find Full Text PDFJ Vis Exp
May 2012
College of Science and Technology, Temple University.
In 1962, R.B. Merrifield published the first procedure using solid-phase peptide synthesis as a novel route to efficiently synthesize peptides.
View Article and Find Full Text PDFACS Nano
September 2008
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
We demonstrate the synthesis of a series of spin-labeled curved oligomers to determine their end-to-end lengths and distance distributions using electron spin resonance. We synthesize shape-persistent macromolecules from conformationally restricted, asymmetric monomers that are coupled through pairs of amide bonds to create water-soluble, spiro-ladder oligomers with well-defined three-dimensional structures. We synthesized seven different macromolecules, each containing eight monomers but differing in the sequence to create macromolecules with different curved shapes.
View Article and Find Full Text PDFJ Org Chem
November 2006
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
We have developed second-generation monomers 1 and 2 and improved conditions for rapidly and simultaneously closing multiple diketopiperazines on solid support. These new conditions involve either the microwave heating of a suspension of solid-supported amino-tetrafluoropropyl esters in acetic acid/triethylamine catalyst solution or continuous flow of catalyst solution through the resin, heated in a flow cell apparatus. We demonstrate that the new monomers 1 and 2 can be combined with the new conditions easily to synthesize previously inaccessible hetero and homo spiro ladder oligomers 3 and 4 and others.
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