β- and γ-amino acids at α-helical interfaces: Toward the formation of highly stable foldameric coiled coils

Elisabeth K. Nyakatura, Jérémie Mortier, Vanessa S. Radtke, Sebastian Wieczorek, Raheleh Rezaei Araghi, Carsten Baldauf, Gerhard Wolber, Beate Koksch

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Since peptides are vital for cellular and pathogenic processes, much effort has been put into the design of unnatural oligomers that mimic natural peptide structures, also referred to as foldamers. However, to enable the specific application of foldamers, a thorough characterization of their interaction profiles in native protein environments is required. We report here the application of phage display for the identification of suitable helical environments for a sequence comprising an alternating set of β- and γ-amino acids. In vitro selected sequences show that an increase in the hydrophobic surface area at the helical interface as well as the incorporation of a polar H-bond donor functionality can significantly improve interhelical interactions involving backbone-extended amino acids. Thus, our data provide insight into the principles of the rational design of foldameric inhibitors for protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)1300-1303
Number of pages4
JournalACS Medicinal Chemistry Letters
Volume5
Issue number12
DOIs
StatePublished - Dec 11 2014
Externally publishedYes

Fingerprint

Amino Acids
Peptides
Proteins
Bacteriophages
Oligomers
Display devices
In Vitro Techniques

Keywords

  • chimeric peptides
  • Phage display
  • βγ amino acids

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

β- and γ-amino acids at α-helical interfaces : Toward the formation of highly stable foldameric coiled coils. / Nyakatura, Elisabeth K.; Mortier, Jérémie; Radtke, Vanessa S.; Wieczorek, Sebastian; Rezaei Araghi, Raheleh; Baldauf, Carsten; Wolber, Gerhard; Koksch, Beate.

In: ACS Medicinal Chemistry Letters, Vol. 5, No. 12, 11.12.2014, p. 1300-1303.

Research output: Contribution to journalArticle

Nyakatura, EK, Mortier, J, Radtke, VS, Wieczorek, S, Rezaei Araghi, R, Baldauf, C, Wolber, G & Koksch, B 2014, 'β- and γ-amino acids at α-helical interfaces: Toward the formation of highly stable foldameric coiled coils', ACS Medicinal Chemistry Letters, vol. 5, no. 12, pp. 1300-1303. https://doi.org/10.1021/ml500361c
Nyakatura, Elisabeth K. ; Mortier, Jérémie ; Radtke, Vanessa S. ; Wieczorek, Sebastian ; Rezaei Araghi, Raheleh ; Baldauf, Carsten ; Wolber, Gerhard ; Koksch, Beate. / β- and γ-amino acids at α-helical interfaces : Toward the formation of highly stable foldameric coiled coils. In: ACS Medicinal Chemistry Letters. 2014 ; Vol. 5, No. 12. pp. 1300-1303.
@article{5209a1e846fc43d7a9d62ac1065c2e9c,
title = "β- and γ-amino acids at α-helical interfaces: Toward the formation of highly stable foldameric coiled coils",
abstract = "Since peptides are vital for cellular and pathogenic processes, much effort has been put into the design of unnatural oligomers that mimic natural peptide structures, also referred to as foldamers. However, to enable the specific application of foldamers, a thorough characterization of their interaction profiles in native protein environments is required. We report here the application of phage display for the identification of suitable helical environments for a sequence comprising an alternating set of β- and γ-amino acids. In vitro selected sequences show that an increase in the hydrophobic surface area at the helical interface as well as the incorporation of a polar H-bond donor functionality can significantly improve interhelical interactions involving backbone-extended amino acids. Thus, our data provide insight into the principles of the rational design of foldameric inhibitors for protein-protein interactions.",
keywords = "chimeric peptides, Phage display, βγ amino acids",
author = "Nyakatura, {Elisabeth K.} and J{\'e}r{\'e}mie Mortier and Radtke, {Vanessa S.} and Sebastian Wieczorek and {Rezaei Araghi}, Raheleh and Carsten Baldauf and Gerhard Wolber and Beate Koksch",
year = "2014",
month = "12",
day = "11",
doi = "10.1021/ml500361c",
language = "English (US)",
volume = "5",
pages = "1300--1303",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - β- and γ-amino acids at α-helical interfaces

T2 - Toward the formation of highly stable foldameric coiled coils

AU - Nyakatura, Elisabeth K.

AU - Mortier, Jérémie

AU - Radtke, Vanessa S.

AU - Wieczorek, Sebastian

AU - Rezaei Araghi, Raheleh

AU - Baldauf, Carsten

AU - Wolber, Gerhard

AU - Koksch, Beate

PY - 2014/12/11

Y1 - 2014/12/11

N2 - Since peptides are vital for cellular and pathogenic processes, much effort has been put into the design of unnatural oligomers that mimic natural peptide structures, also referred to as foldamers. However, to enable the specific application of foldamers, a thorough characterization of their interaction profiles in native protein environments is required. We report here the application of phage display for the identification of suitable helical environments for a sequence comprising an alternating set of β- and γ-amino acids. In vitro selected sequences show that an increase in the hydrophobic surface area at the helical interface as well as the incorporation of a polar H-bond donor functionality can significantly improve interhelical interactions involving backbone-extended amino acids. Thus, our data provide insight into the principles of the rational design of foldameric inhibitors for protein-protein interactions.

AB - Since peptides are vital for cellular and pathogenic processes, much effort has been put into the design of unnatural oligomers that mimic natural peptide structures, also referred to as foldamers. However, to enable the specific application of foldamers, a thorough characterization of their interaction profiles in native protein environments is required. We report here the application of phage display for the identification of suitable helical environments for a sequence comprising an alternating set of β- and γ-amino acids. In vitro selected sequences show that an increase in the hydrophobic surface area at the helical interface as well as the incorporation of a polar H-bond donor functionality can significantly improve interhelical interactions involving backbone-extended amino acids. Thus, our data provide insight into the principles of the rational design of foldameric inhibitors for protein-protein interactions.

KW - chimeric peptides

KW - Phage display

KW - βγ amino acids

UR - http://www.scopus.com/inward/record.url?scp=84918528185&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918528185&partnerID=8YFLogxK

U2 - 10.1021/ml500361c

DO - 10.1021/ml500361c

M3 - Article

AN - SCOPUS:84918528185

VL - 5

SP - 1300

EP - 1303

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

IS - 12

ER -