Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides

Takahiro Tsukida, Hideki Moriyama, Kiriko Kurokawa, Toshio Achiha, Yoshimasa Inoue, Hirosato Kondo

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(X), 1) and a 3'sulfated Lewis X analogue (2) toward E- selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' β-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' β-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(X) mimetics with type II and type II' β-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

Original languageEnglish
Pages (from-to)4279-4287
Number of pages9
JournalJournal of Medicinal Chemistry
Volume41
Issue number22
DOIs
Publication statusPublished - Oct 23 1998
Externally publishedYes

Fingerprint

Selectins
E-Selectin
Dipeptides
Structure-Activity Relationship
Molecular Dynamics Simulation
serine containing aminolipid

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides. / Tsukida, Takahiro; Moriyama, Hideki; Kurokawa, Kiriko; Achiha, Toshio; Inoue, Yoshimasa; Kondo, Hirosato.

In: Journal of Medicinal Chemistry, Vol. 41, No. 22, 23.10.1998, p. 4279-4287.

Research output: Contribution to journalArticle

Tsukida, Takahiro ; Moriyama, Hideki ; Kurokawa, Kiriko ; Achiha, Toshio ; Inoue, Yoshimasa ; Kondo, Hirosato. / Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides. In: Journal of Medicinal Chemistry. 1998 ; Vol. 41, No. 22. pp. 4279-4287.
@article{a61cdb2fe83c4e7783a4646e44270ac5,
title = "Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides",
abstract = "We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(X), 1) and a 3'sulfated Lewis X analogue (2) toward E- selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' β-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' β-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(X) mimetics with type II and type II' β-turn dipeptides could be a useful methodology for the design of an active selectin blocker.",
author = "Takahiro Tsukida and Hideki Moriyama and Kiriko Kurokawa and Toshio Achiha and Yoshimasa Inoue and Hirosato Kondo",
year = "1998",
month = "10",
day = "23",
doi = "10.1021/jm980267x",
language = "English",
volume = "41",
pages = "4279--4287",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "22",

}

TY - JOUR

T1 - Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified ser-glu dipeptides

AU - Tsukida, Takahiro

AU - Moriyama, Hideki

AU - Kurokawa, Kiriko

AU - Achiha, Toshio

AU - Inoue, Yoshimasa

AU - Kondo, Hirosato

PY - 1998/10/23

Y1 - 1998/10/23

N2 - We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(X), 1) and a 3'sulfated Lewis X analogue (2) toward E- selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' β-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' β-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(X) mimetics with type II and type II' β-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

AB - We have previously found that heterochiral fucodipeptides, L-Ser-D-Glu (3a) and D-Ser-L-Glu (3b), exhibited up to 20-100 times more potency than a sialyl Lewis X (sLe(X), 1) and a 3'sulfated Lewis X analogue (2) toward E- selectin binding and have also proposed, from molecular dynamics calculation, that their strong activities would depend on a possible formation of the type II and/or type II' β-turn of compounds 3a,b (Tsukida, T.; Hiramatsu, Y.; Tsujishita, H.; Kiyoi, T.; Yoshida, M.; Kurokawa, K.; Moriyama, H.; Ohmoto, H.; Wada, Y.; Saito, T.; Kondo, H. J. Med. Chem. 1997, 40, 3534-3541). To clarify our hypothesis, we synthesized several analogues of compounds 3a,b and investigated their structure-activity relationships. As a result, it was indicated that the type II and/or type II' β-turn conformation would be a comparatively tight form and would play important roles in favorable binding to E-selectin. These findings indicate that sLe(X) mimetics with type II and type II' β-turn dipeptides could be a useful methodology for the design of an active selectin blocker.

UR - http://www.scopus.com/inward/record.url?scp=0032561222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032561222&partnerID=8YFLogxK

U2 - 10.1021/jm980267x

DO - 10.1021/jm980267x

M3 - Article

C2 - 9784103

AN - SCOPUS:0032561222

VL - 41

SP - 4279

EP - 4287

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 22

ER -