Journal article

alpha/beta-Peptide Foldamers Targeting Intracellular Protein-Protein Interactions with Activity in Living Cells

James W Checco, Erinna F Lee, Marco Evangelista, Nerida J Sleebs, Kelly Rogers, Anne Pettikiriarachchi, Nadia J Kershaw, Geoffrey A Eddinger, David G Belair, Julia L Wilson, Chelcie H Eller, Ronald T Raines, William L Murphy, Brian J Smith, Samuel H Gellman, W Douglas Fairlie

Journal of the American Chemical Society | AMER CHEMICAL SOC | Published : 2015

Abstract

Peptides can be developed as effective antagonists of protein-protein interactions, but conventional peptides (i.e., oligomers of l-α-amino acids) suffer from significant limitations in vivo. Short half-lives due to rapid proteolytic degradation and an inability to cross cell membranes often preclude biological applications of peptides. Oligomers that contain both α- and β-amino acid residues ("α/β-peptides") manifest decreased susceptibility to proteolytic degradation, and when properly designed these unnatural oligomers can mimic the protein-recognition properties of analogous "α-peptides". This report documents an extension of the α/β-peptide approach to target intracellular protein-prote..

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Grants

Awarded by NIGMS


Awarded by NHMRC of Australia


Awarded by Cancer Council Victoria


Awarded by NHMRC IRIISS


Awarded by NIH


Awarded by University of Wisconsin-Madison Nanoscale Science and Engineering Center


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

This research was supported by NIGMS (GM056414, to S.H.G.) and grants and fellowships from the NHMRC of Australia (Project Grant 1041936, to W.D.F., and Career Development Fellowship 1024620, to E.F.L.) and Cancer Council Victoria (Grant-in-aid 1057949). Infrastructure support from NHMRC IRIISS grant no. 361646 and the Victorian State Government OIS grant is gratefully acknowledged. J.W.C. was supported in part by a Biotechnology Training Grant (NIH Grant T32 GM008349). Additional support was provided by NIH (HL093282, to W.L.M., and GM044783, to R.T.R.). In addition, W.L.M. acknowledges support from the University of Wisconsin-Madison Nanoscale Science and Engineering Center (DMR-0832760).