Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE

Daniel A. Offermann; John E. McKendrick; Jimmy J. P. Sejberg; Bingli Mo; Mary D. Holdom; Birgit A. Helm; Robin J. Leatherbarrow; Andrew J. Beavil; Brian J. Sutton; Alan C. Spivey

doi:10.1021/jo202604q

Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE

Daniel A. Offermann, John E. McKendrick, Jimmy J. P. Sejberg, Bingli Mo, Mary D. Holdom, Birgit A. Helm, Robin J. Leatherbarrow, Andrew J. Beavil, Brian J. Sutton, Alan C. Spivey

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20 Citations (Scopus)

Abstract

The disruption of the human immunolobulin E-high affinity receptor I (IgE-Fc epsilon RI) protein-protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the C epsilon 3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 similar to 660 mu M) is displayed by the peptide containing a 2,2'-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.

Original language	English
Pages (from-to)	3197 - 3214
Number of pages	18
Journal	JOURNAL OF ORGANIC CHEMISTRY
Volume	77
Issue number	7
DOIs	https://doi.org/10.1021/jo202604q
Publication status	Published - 6 Apr 2012

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Offermann, D. A., McKendrick, J. E., Sejberg, J. J. P., Mo, B., Holdom, M. D., Helm, B. A., Leatherbarrow, R. J., Beavil, A. J., Sutton, B. J., & Spivey, A. C. (2012). Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE. JOURNAL OF ORGANIC CHEMISTRY, 77(7), 3197 - 3214. https://doi.org/10.1021/jo202604q

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title = "Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE",

abstract = "The disruption of the human immunolobulin E-high affinity receptor I (IgE-Fc epsilon RI) protein-protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the C epsilon 3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 similar to 660 mu M) is displayed by the peptide containing a 2,2'-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.",

author = "Offermann, {Daniel A.} and McKendrick, {John E.} and Sejberg, {Jimmy J. P.} and Bingli Mo and Holdom, {Mary D.} and Helm, {Birgit A.} and Leatherbarrow, {Robin J.} and Beavil, {Andrew J.} and Sutton, {Brian J.} and Spivey, {Alan C.}",

year = "2012",

month = apr,

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doi = "10.1021/jo202604q",

language = "English",

volume = "77",

pages = "3197 -- 3214",

journal = "JOURNAL OF ORGANIC CHEMISTRY",

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Offermann, DA, McKendrick, JE, Sejberg, JJP, Mo, B, Holdom, MD, Helm, BA, Leatherbarrow, RJ, Beavil, AJ , Sutton, BJ & Spivey, AC 2012, 'Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE', JOURNAL OF ORGANIC CHEMISTRY, vol. 77, no. 7, pp. 3197 - 3214. https://doi.org/10.1021/jo202604q

Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE. / Offermann, Daniel A.; McKendrick, John E.; Sejberg, Jimmy J. P. et al.
In: JOURNAL OF ORGANIC CHEMISTRY, Vol. 77, No. 7, 06.04.2012, p. 3197 - 3214.

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

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AU - McKendrick, John E.

AU - Sejberg, Jimmy J. P.

AU - Mo, Bingli

AU - Holdom, Mary D.

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AU - Sutton, Brian J.

AU - Spivey, Alan C.

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AB - The disruption of the human immunolobulin E-high affinity receptor I (IgE-Fc epsilon RI) protein-protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the C epsilon 3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 similar to 660 mu M) is displayed by the peptide containing a 2,2'-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.

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Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE

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