Encoding Method for OBOC Small Molecule Libraries Using a Biphasic Approach for Ladder-Synthesis of Coding Tags

Xiaobing Wang, Jinhua Zhang, Aimin Song, Carlito B Lebrilla, Kit Lam

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

In the "one-bead one-compound" (OBOC) combinatorial library method, each compound bead displays only one compound entity. Hundreds of thousands to millions of compound beads can be synthesized rapidly and screened simultaneously. Positive compound beads are then isolated for structural analysis. To fully exploit the power of OBOC combinatorial small molecule libraries, a robust and high throughput encoding method is needed to decode the positive compound beads. In this paper, we report on the development of a novel encoding strategy that combines the concepts of ladder-synthesis and chemical encoding on bilayer beads. In these encoded libraries, small molecule compounds are displayed on the bead surface, and cleavable coding tags consisting of a series of truncated molecules reside in the bead interior. Such a library can be easily constructed using the biphasic approach (J. Am. Chem. Soc. 2002, 124, 7678) to topologically segregate the functionalities of the beads during library synthesis. The ladder members and coding tags are then released for MALDI-TOF-MS analysis. To simplify the interpretation of the mass spectra, we purposely add bromine into the cleavable linker so that the cleavage products generate a characteristic isotope fingerprint. The chemical structure of library compounds can be determined by analyzing the mass differences between adjacent peaks on the mass spectra. This encoding strategy also provides valuable information on the quality of the testing compound on the surface of the bead. To validate this methodology, a model OBOC small molecule library with 12,288 members was synthesized on TentaGel beads and screened against streptavidin. The chemical structures of the compound on each positive bead were unambiguously identified.

Original languageEnglish (US)
Pages (from-to)5740-5749
Number of pages10
JournalJournal of the American Chemical Society
Volume126
Issue number18
DOIs
StatePublished - May 12 2004

Fingerprint

Small Molecule Libraries
Ladders
Molecules
Bromine
Streptavidin
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Dermatoglyphics
Interiors (building)
Isotopes
Libraries
Structural analysis
Throughput
Testing

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Encoding Method for OBOC Small Molecule Libraries Using a Biphasic Approach for Ladder-Synthesis of Coding Tags. / Wang, Xiaobing; Zhang, Jinhua; Song, Aimin; Lebrilla, Carlito B; Lam, Kit.

In: Journal of the American Chemical Society, Vol. 126, No. 18, 12.05.2004, p. 5740-5749.

Research output: Contribution to journalArticle

Wang, Xiaobing ; Zhang, Jinhua ; Song, Aimin ; Lebrilla, Carlito B ; Lam, Kit. / Encoding Method for OBOC Small Molecule Libraries Using a Biphasic Approach for Ladder-Synthesis of Coding Tags. In: Journal of the American Chemical Society. 2004 ; Vol. 126, No. 18. pp. 5740-5749.
@article{a62b8e173ea94f739c3705383cb602bd,
title = "Encoding Method for OBOC Small Molecule Libraries Using a Biphasic Approach for Ladder-Synthesis of Coding Tags",
abstract = "In the {"}one-bead one-compound{"} (OBOC) combinatorial library method, each compound bead displays only one compound entity. Hundreds of thousands to millions of compound beads can be synthesized rapidly and screened simultaneously. Positive compound beads are then isolated for structural analysis. To fully exploit the power of OBOC combinatorial small molecule libraries, a robust and high throughput encoding method is needed to decode the positive compound beads. In this paper, we report on the development of a novel encoding strategy that combines the concepts of ladder-synthesis and chemical encoding on bilayer beads. In these encoded libraries, small molecule compounds are displayed on the bead surface, and cleavable coding tags consisting of a series of truncated molecules reside in the bead interior. Such a library can be easily constructed using the biphasic approach (J. Am. Chem. Soc. 2002, 124, 7678) to topologically segregate the functionalities of the beads during library synthesis. The ladder members and coding tags are then released for MALDI-TOF-MS analysis. To simplify the interpretation of the mass spectra, we purposely add bromine into the cleavable linker so that the cleavage products generate a characteristic isotope fingerprint. The chemical structure of library compounds can be determined by analyzing the mass differences between adjacent peaks on the mass spectra. This encoding strategy also provides valuable information on the quality of the testing compound on the surface of the bead. To validate this methodology, a model OBOC small molecule library with 12,288 members was synthesized on TentaGel beads and screened against streptavidin. The chemical structures of the compound on each positive bead were unambiguously identified.",
author = "Xiaobing Wang and Jinhua Zhang and Aimin Song and Lebrilla, {Carlito B} and Kit Lam",
year = "2004",
month = "5",
day = "12",
doi = "10.1021/ja049322j",
language = "English (US)",
volume = "126",
pages = "5740--5749",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "18",

}

TY - JOUR

T1 - Encoding Method for OBOC Small Molecule Libraries Using a Biphasic Approach for Ladder-Synthesis of Coding Tags

AU - Wang, Xiaobing

AU - Zhang, Jinhua

AU - Song, Aimin

AU - Lebrilla, Carlito B

AU - Lam, Kit

PY - 2004/5/12

Y1 - 2004/5/12

N2 - In the "one-bead one-compound" (OBOC) combinatorial library method, each compound bead displays only one compound entity. Hundreds of thousands to millions of compound beads can be synthesized rapidly and screened simultaneously. Positive compound beads are then isolated for structural analysis. To fully exploit the power of OBOC combinatorial small molecule libraries, a robust and high throughput encoding method is needed to decode the positive compound beads. In this paper, we report on the development of a novel encoding strategy that combines the concepts of ladder-synthesis and chemical encoding on bilayer beads. In these encoded libraries, small molecule compounds are displayed on the bead surface, and cleavable coding tags consisting of a series of truncated molecules reside in the bead interior. Such a library can be easily constructed using the biphasic approach (J. Am. Chem. Soc. 2002, 124, 7678) to topologically segregate the functionalities of the beads during library synthesis. The ladder members and coding tags are then released for MALDI-TOF-MS analysis. To simplify the interpretation of the mass spectra, we purposely add bromine into the cleavable linker so that the cleavage products generate a characteristic isotope fingerprint. The chemical structure of library compounds can be determined by analyzing the mass differences between adjacent peaks on the mass spectra. This encoding strategy also provides valuable information on the quality of the testing compound on the surface of the bead. To validate this methodology, a model OBOC small molecule library with 12,288 members was synthesized on TentaGel beads and screened against streptavidin. The chemical structures of the compound on each positive bead were unambiguously identified.

AB - In the "one-bead one-compound" (OBOC) combinatorial library method, each compound bead displays only one compound entity. Hundreds of thousands to millions of compound beads can be synthesized rapidly and screened simultaneously. Positive compound beads are then isolated for structural analysis. To fully exploit the power of OBOC combinatorial small molecule libraries, a robust and high throughput encoding method is needed to decode the positive compound beads. In this paper, we report on the development of a novel encoding strategy that combines the concepts of ladder-synthesis and chemical encoding on bilayer beads. In these encoded libraries, small molecule compounds are displayed on the bead surface, and cleavable coding tags consisting of a series of truncated molecules reside in the bead interior. Such a library can be easily constructed using the biphasic approach (J. Am. Chem. Soc. 2002, 124, 7678) to topologically segregate the functionalities of the beads during library synthesis. The ladder members and coding tags are then released for MALDI-TOF-MS analysis. To simplify the interpretation of the mass spectra, we purposely add bromine into the cleavable linker so that the cleavage products generate a characteristic isotope fingerprint. The chemical structure of library compounds can be determined by analyzing the mass differences between adjacent peaks on the mass spectra. This encoding strategy also provides valuable information on the quality of the testing compound on the surface of the bead. To validate this methodology, a model OBOC small molecule library with 12,288 members was synthesized on TentaGel beads and screened against streptavidin. The chemical structures of the compound on each positive bead were unambiguously identified.

UR - http://www.scopus.com/inward/record.url?scp=2442431392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442431392&partnerID=8YFLogxK

U2 - 10.1021/ja049322j

DO - 10.1021/ja049322j

M3 - Article

C2 - 15125667

AN - SCOPUS:2442431392

VL - 126

SP - 5740

EP - 5749

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 18

ER -