Enantioselective synthesis of an unnatural bipyridyl amino acid and its incorporation into a peptide

Kenneth J. Kise; Bruce E. Bowler

doi:10.1016/S0957-4166(98)00350-4

Enantioselective synthesis of an unnatural bipyridyl amino acid and its incorporation into a peptide

Kenneth J. Kise
, Bruce E. Bowler

Chemistry and Biochemistry

University of Denver

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

The synthesis of a bipyridyl amino acid, 2-amino-3-(4'-methyl-2,2'- bipyridin-4-yl) propanoic acid, is described. A short three step synthesis from commercially available 4,4'-dimethyl-2,2'-bipyridine provides the amino acid in 65% enantiomeric excess (ee). An enzyme-mediated chiral resolution increases the ee to 95% in two additional steps. The amino acid was incorporated into a 22 amino acid peptide composed predominantly of alanine. The peptide was found to be 88% α-helical in aqueous solution at 1°C by circular dichroism (CD) spectropolarimetry, indicating a high helical propensity for this amino acid. This amino acid can provide a means to incorporate a metal into structure-forming peptides.

Original language	English
Pages (from-to)	3319-3324
Number of pages	6
Journal	Tetrahedron Asymmetry
Volume	9
Issue number	18
DOIs	https://doi.org/10.1016/S0957-4166(98)00350-4
State	Published - Sep 18 1998

Funding

We wish to thank John Stewart and Eunice York from the University of Colorado Health Sciences Center for their assistance with peptide synthesis, MALDI-TOF mass spectrometry, and for use of their polarimeter. Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for support of this work.

Funders
American Chemical Society

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10.1016/S0957-4166(98)00350-4

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title = "Enantioselective synthesis of an unnatural bipyridyl amino acid and its incorporation into a peptide",

abstract = "The synthesis of a bipyridyl amino acid, 2-amino-3-(4'-methyl-2,2'- bipyridin-4-yl) propanoic acid, is described. A short three step synthesis from commercially available 4,4'-dimethyl-2,2'-bipyridine provides the amino acid in 65\% enantiomeric excess (ee). An enzyme-mediated chiral resolution increases the ee to 95\% in two additional steps. The amino acid was incorporated into a 22 amino acid peptide composed predominantly of alanine. The peptide was found to be 88\% α-helical in aqueous solution at 1°C by circular dichroism (CD) spectropolarimetry, indicating a high helical propensity for this amino acid. This amino acid can provide a means to incorporate a metal into structure-forming peptides.",

author = "Kise, \{Kenneth J.\} and Bowler, \{Bruce E.\}",

note = "Funding Information: We wish to thank John Stewart and Eunice York from the University of Colorado Health Sciences Center for their assistance with peptide synthesis, MALDI-TOF mass spectrometry, and for use of their polarimeter. Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for support of this work.",

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doi = "10.1016/S0957-4166(98)00350-4",

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T1 - Enantioselective synthesis of an unnatural bipyridyl amino acid and its incorporation into a peptide

AU - Kise, Kenneth J.

AU - Bowler, Bruce E.

N1 - Funding Information: We wish to thank John Stewart and Eunice York from the University of Colorado Health Sciences Center for their assistance with peptide synthesis, MALDI-TOF mass spectrometry, and for use of their polarimeter. Acknowledgment is made to the donors of the Petroleum Research Fund, administered by the American Chemical Society, for support of this work.

PY - 1998/9/18

Y1 - 1998/9/18

N2 - The synthesis of a bipyridyl amino acid, 2-amino-3-(4'-methyl-2,2'- bipyridin-4-yl) propanoic acid, is described. A short three step synthesis from commercially available 4,4'-dimethyl-2,2'-bipyridine provides the amino acid in 65% enantiomeric excess (ee). An enzyme-mediated chiral resolution increases the ee to 95% in two additional steps. The amino acid was incorporated into a 22 amino acid peptide composed predominantly of alanine. The peptide was found to be 88% α-helical in aqueous solution at 1°C by circular dichroism (CD) spectropolarimetry, indicating a high helical propensity for this amino acid. This amino acid can provide a means to incorporate a metal into structure-forming peptides.

AB - The synthesis of a bipyridyl amino acid, 2-amino-3-(4'-methyl-2,2'- bipyridin-4-yl) propanoic acid, is described. A short three step synthesis from commercially available 4,4'-dimethyl-2,2'-bipyridine provides the amino acid in 65% enantiomeric excess (ee). An enzyme-mediated chiral resolution increases the ee to 95% in two additional steps. The amino acid was incorporated into a 22 amino acid peptide composed predominantly of alanine. The peptide was found to be 88% α-helical in aqueous solution at 1°C by circular dichroism (CD) spectropolarimetry, indicating a high helical propensity for this amino acid. This amino acid can provide a means to incorporate a metal into structure-forming peptides.

UR - https://www.scopus.com/pages/publications/0032544781

U2 - 10.1016/S0957-4166(98)00350-4

DO - 10.1016/S0957-4166(98)00350-4

M3 - Article

AN - SCOPUS:0032544781

SN - 0957-4166

VL - 9

SP - 3319

EP - 3324

JO - Tetrahedron Asymmetry

JF - Tetrahedron Asymmetry

IS - 18

ER -

Enantioselective synthesis of an unnatural bipyridyl amino acid and its incorporation into a peptide

Abstract

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