Coupling difficulty following replacement of Tyr with HOTic during synthesis of an analog of an EGF B-loop fragment

F. Ötvös, R. F. Murphy, Sándor Lovas

Research output: Article

6 Citations (Scopus)

Abstract

During Fmoc synthesis of an analog, [Abu20,31, HOTic22]hEGF(20- 31), of a fragment, Cys-Met-Tyr-Ile-Glu-Ala-Leu-Asp-Lys-Tyr-Ala-Cys, of the B-loop of human EGF, conductivity measurements showed that increased time was necessary for coupling and complete deprotection of the residues Met21 and Abu20 which followed the HOTic22. Use of different active ester-forming reagents, including HOBt and BOP, did not increase the yield. Use of symmetrical anhydride with extended coupling time increased the yield but did not complete the coupling. It appears that inclusion of HOTic in place of Tyr to introduce conformational constraint to peptide analogs can cause or augment a tendency towards conformations with increasing occlusion of N- terminal amino groups and result in the need for altered coupling strategies for completion of analog synthesis.

Original languageEnglish
Pages (from-to)302-307
Number of pages6
JournalJournal of Peptide Research
Volume53
Issue number3
DOIs
Publication statusPublished - 1999

Fingerprint

Epidermal Growth Factor
Anhydrides
Conformations
Esters
Peptides
1-hydroxybenzotriazole

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

@article{e8ac4bbf614e48abba667d80be728bf5,
title = "Coupling difficulty following replacement of Tyr with HOTic during synthesis of an analog of an EGF B-loop fragment",
abstract = "During Fmoc synthesis of an analog, [Abu20,31, HOTic22]hEGF(20- 31), of a fragment, Cys-Met-Tyr-Ile-Glu-Ala-Leu-Asp-Lys-Tyr-Ala-Cys, of the B-loop of human EGF, conductivity measurements showed that increased time was necessary for coupling and complete deprotection of the residues Met21 and Abu20 which followed the HOTic22. Use of different active ester-forming reagents, including HOBt and BOP, did not increase the yield. Use of symmetrical anhydride with extended coupling time increased the yield but did not complete the coupling. It appears that inclusion of HOTic in place of Tyr to introduce conformational constraint to peptide analogs can cause or augment a tendency towards conformations with increasing occlusion of N- terminal amino groups and result in the need for altered coupling strategies for completion of analog synthesis.",
keywords = "7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, Coupling difficulty, Fmoc chemistry, HOTic, Peptide synthesis, Tic",
author = "F. {\"O}tv{\"o}s and Murphy, {R. F.} and S{\'a}ndor Lovas",
year = "1999",
doi = "10.1034/j.1399-3011.1999.00026.x",
language = "English",
volume = "53",
pages = "302--307",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",
number = "3",

}

TY - JOUR

T1 - Coupling difficulty following replacement of Tyr with HOTic during synthesis of an analog of an EGF B-loop fragment

AU - Ötvös, F.

AU - Murphy, R. F.

AU - Lovas, Sándor

PY - 1999

Y1 - 1999

N2 - During Fmoc synthesis of an analog, [Abu20,31, HOTic22]hEGF(20- 31), of a fragment, Cys-Met-Tyr-Ile-Glu-Ala-Leu-Asp-Lys-Tyr-Ala-Cys, of the B-loop of human EGF, conductivity measurements showed that increased time was necessary for coupling and complete deprotection of the residues Met21 and Abu20 which followed the HOTic22. Use of different active ester-forming reagents, including HOBt and BOP, did not increase the yield. Use of symmetrical anhydride with extended coupling time increased the yield but did not complete the coupling. It appears that inclusion of HOTic in place of Tyr to introduce conformational constraint to peptide analogs can cause or augment a tendency towards conformations with increasing occlusion of N- terminal amino groups and result in the need for altered coupling strategies for completion of analog synthesis.

AB - During Fmoc synthesis of an analog, [Abu20,31, HOTic22]hEGF(20- 31), of a fragment, Cys-Met-Tyr-Ile-Glu-Ala-Leu-Asp-Lys-Tyr-Ala-Cys, of the B-loop of human EGF, conductivity measurements showed that increased time was necessary for coupling and complete deprotection of the residues Met21 and Abu20 which followed the HOTic22. Use of different active ester-forming reagents, including HOBt and BOP, did not increase the yield. Use of symmetrical anhydride with extended coupling time increased the yield but did not complete the coupling. It appears that inclusion of HOTic in place of Tyr to introduce conformational constraint to peptide analogs can cause or augment a tendency towards conformations with increasing occlusion of N- terminal amino groups and result in the need for altered coupling strategies for completion of analog synthesis.

KW - 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

KW - Coupling difficulty

KW - Fmoc chemistry

KW - HOTic

KW - Peptide synthesis

KW - Tic

UR - http://www.scopus.com/inward/record.url?scp=0032951934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032951934&partnerID=8YFLogxK

U2 - 10.1034/j.1399-3011.1999.00026.x

DO - 10.1034/j.1399-3011.1999.00026.x

M3 - Article

C2 - 10231718

AN - SCOPUS:0032951934

VL - 53

SP - 302

EP - 307

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

SN - 1747-0277

IS - 3

ER -