Environment-independent 14-helix formation in short β-peptides

Striking a balance between shape control and functional diversity

Tami L. Raguse, Jonathan R. Lai, Samuel H. Gellman

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

We report a significant and unanticipated advance in the study of β-amino acid-based foldamers: a small proportion of highly preorganized residues can impart high stability to a specific helical secondary structure in water. Most of the residues in these β-peptides (2 and 3) are intrinsically flexible. Flexible β-amino acids can be readily and enantiospecifically prepared in functionally diverse forms, but preorganized residues with side chains are rare and challenging to synthesize. Our findings demonstrate that interspersing a few copies of an unfunctionalized but rigid residue among a larger number of flexible residues with diverse side chains is a viable strategy for creating β-peptides that adopt the 14-helix conformation and therefore display side chains in a predictable spatial arrangement. These results are significant because they enhance the prospects of developing β-peptides with useful activities.

Original languageEnglish (US)
Pages (from-to)5592-5593
Number of pages2
JournalJournal of the American Chemical Society
Volume125
Issue number19
DOIs
StatePublished - May 14 2003
Externally publishedYes

Fingerprint

Peptides
Amino acids
Amino Acids
Conformations
Water

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Environment-independent 14-helix formation in short β-peptides : Striking a balance between shape control and functional diversity. / Raguse, Tami L.; Lai, Jonathan R.; Gellman, Samuel H.

In: Journal of the American Chemical Society, Vol. 125, No. 19, 14.05.2003, p. 5592-5593.

Research output: Contribution to journalArticle

@article{4e658354d830414fb5edeb34ac43e040,
title = "Environment-independent 14-helix formation in short β-peptides: Striking a balance between shape control and functional diversity",
abstract = "We report a significant and unanticipated advance in the study of β-amino acid-based foldamers: a small proportion of highly preorganized residues can impart high stability to a specific helical secondary structure in water. Most of the residues in these β-peptides (2 and 3) are intrinsically flexible. Flexible β-amino acids can be readily and enantiospecifically prepared in functionally diverse forms, but preorganized residues with side chains are rare and challenging to synthesize. Our findings demonstrate that interspersing a few copies of an unfunctionalized but rigid residue among a larger number of flexible residues with diverse side chains is a viable strategy for creating β-peptides that adopt the 14-helix conformation and therefore display side chains in a predictable spatial arrangement. These results are significant because they enhance the prospects of developing β-peptides with useful activities.",
author = "Raguse, {Tami L.} and Lai, {Jonathan R.} and Gellman, {Samuel H.}",
year = "2003",
month = "5",
day = "14",
doi = "10.1021/ja0341485",
language = "English (US)",
volume = "125",
pages = "5592--5593",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "19",

}

TY - JOUR

T1 - Environment-independent 14-helix formation in short β-peptides

T2 - Striking a balance between shape control and functional diversity

AU - Raguse, Tami L.

AU - Lai, Jonathan R.

AU - Gellman, Samuel H.

PY - 2003/5/14

Y1 - 2003/5/14

N2 - We report a significant and unanticipated advance in the study of β-amino acid-based foldamers: a small proportion of highly preorganized residues can impart high stability to a specific helical secondary structure in water. Most of the residues in these β-peptides (2 and 3) are intrinsically flexible. Flexible β-amino acids can be readily and enantiospecifically prepared in functionally diverse forms, but preorganized residues with side chains are rare and challenging to synthesize. Our findings demonstrate that interspersing a few copies of an unfunctionalized but rigid residue among a larger number of flexible residues with diverse side chains is a viable strategy for creating β-peptides that adopt the 14-helix conformation and therefore display side chains in a predictable spatial arrangement. These results are significant because they enhance the prospects of developing β-peptides with useful activities.

AB - We report a significant and unanticipated advance in the study of β-amino acid-based foldamers: a small proportion of highly preorganized residues can impart high stability to a specific helical secondary structure in water. Most of the residues in these β-peptides (2 and 3) are intrinsically flexible. Flexible β-amino acids can be readily and enantiospecifically prepared in functionally diverse forms, but preorganized residues with side chains are rare and challenging to synthesize. Our findings demonstrate that interspersing a few copies of an unfunctionalized but rigid residue among a larger number of flexible residues with diverse side chains is a viable strategy for creating β-peptides that adopt the 14-helix conformation and therefore display side chains in a predictable spatial arrangement. These results are significant because they enhance the prospects of developing β-peptides with useful activities.

UR - http://www.scopus.com/inward/record.url?scp=0037959630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037959630&partnerID=8YFLogxK

U2 - 10.1021/ja0341485

DO - 10.1021/ja0341485

M3 - Article

VL - 125

SP - 5592

EP - 5593

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 19

ER -