Applications of topologically segregated bilayer beads in 'one-bead one-compound' combinatorial libraries

X. Wang, L. Peng, Ruiwu Liu, B. Xu, Kit Lam

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating One-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.

Original languageEnglish (US)
Pages (from-to)130-138
Number of pages9
JournalJournal of Peptide Research
Volume65
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Peptides
Libraries
Substitution reactions
Ligands
T-Cell Leukemia
Peptide Library
Jurkat Cells
T-cells
Screening
Cells
Cell Line
Testing

Keywords

  • Bilayer beads
  • Library screening
  • One-bead one-compound combinatorial libraries
  • Peptide libraries

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Applications of topologically segregated bilayer beads in 'one-bead one-compound' combinatorial libraries. / Wang, X.; Peng, L.; Liu, Ruiwu; Xu, B.; Lam, Kit.

In: Journal of Peptide Research, Vol. 65, No. 1, 01.2005, p. 130-138.

Research output: Contribution to journalArticle

@article{e5a972024a88425099ba1a87b72f5f03,
title = "Applications of topologically segregated bilayer beads in 'one-bead one-compound' combinatorial libraries",
abstract = "We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating One-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.",
keywords = "Bilayer beads, Library screening, One-bead one-compound combinatorial libraries, Peptide libraries",
author = "X. Wang and L. Peng and Ruiwu Liu and B. Xu and Kit Lam",
year = "2005",
month = "1",
doi = "10.1111/j.1399-3011.2005.00192.x",
language = "English (US)",
volume = "65",
pages = "130--138",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",
number = "1",

}

TY - JOUR

T1 - Applications of topologically segregated bilayer beads in 'one-bead one-compound' combinatorial libraries

AU - Wang, X.

AU - Peng, L.

AU - Liu, Ruiwu

AU - Xu, B.

AU - Lam, Kit

PY - 2005/1

Y1 - 2005/1

N2 - We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating One-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.

AB - We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating One-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.

KW - Bilayer beads

KW - Library screening

KW - One-bead one-compound combinatorial libraries

KW - Peptide libraries

UR - http://www.scopus.com/inward/record.url?scp=14044278111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14044278111&partnerID=8YFLogxK

U2 - 10.1111/j.1399-3011.2005.00192.x

DO - 10.1111/j.1399-3011.2005.00192.x

M3 - Article

C2 - 15686543

AN - SCOPUS:14044278111

VL - 65

SP - 130

EP - 138

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

SN - 1747-0277

IS - 1

ER -