Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries

Ruiwu Liu, Tsung Chieh Shih, Xiaojun Deng, Lara Anwar, Sara Ahadi, Pappanaicken Kumaresan, Kit S. Lam

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The “one-bead two-compound” (OB2C) combinatorial library is constructed on topologically segregated trifunctional bilayer beads such that each bead has a fixed cell-capturing ligand and a random library compound co-displayed on its surface and a chemical coding tag (bar code) inside the bead. An OB2C library containing thousands to millions of compounds can be synthesized and screened concurrently within a short period of time. When live cells are incubated with such OB2C libraries, every bead will be coated with a monolayer of cells. The cell membranes of the captured cells facing the bead surface are exposed to the library compounds tethered to each bead. A specific biochemical or cellular response can be detected with an appropriate reporter system. The OB2C method enables investigators to rapidly discover synthetic molecules that not only interact with cell-surface receptors but can also stimulate or inhibit downstream cell signaling. To demonstrate this powerful method, one OB2C peptide library and two OB2C peptidomimetic libraries were synthesized and screened against Molt-4 lymphoma cells to discover “death ligands.” Apoptosis of the bead-bound cells was detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated anti-cleaved caspase-3 antibody and 3,3′-diaminobenzidine as a substrate. Two novel synthetic “death ligands” against Molt-4 cells were discovered using this OB2C library approach.

Original languageEnglish (US)
Pages (from-to)1-2
Number of pages2
JournalMethods in Molecular Biology
Volume1248
DOIs
StatePublished - 2015

Fingerprint

Peptidomimetics
Peptide Library
Libraries
Ligands
Cell Surface Receptors
Horseradish Peroxidase
Automatic Data Processing
Caspase 3
Lymphoma
Immunohistochemistry
Research Personnel
Cell Membrane
Apoptosis
Antibodies

Keywords

  • Apoptosis
  • Bilayer bead
  • Cell-capturing ligand
  • Immunocytochemistry
  • Lymphoma
  • OB2C combinatorial library
  • Proapoptotic agent
  • Synthetic “death ligand”

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries. / Liu, Ruiwu; Shih, Tsung Chieh; Deng, Xiaojun; Anwar, Lara; Ahadi, Sara; Kumaresan, Pappanaicken; Lam, Kit S.

In: Methods in Molecular Biology, Vol. 1248, 2015, p. 1-2.

Research output: Contribution to journalArticle

Liu, Ruiwu ; Shih, Tsung Chieh ; Deng, Xiaojun ; Anwar, Lara ; Ahadi, Sara ; Kumaresan, Pappanaicken ; Lam, Kit S. / Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries. In: Methods in Molecular Biology. 2015 ; Vol. 1248. pp. 1-2.
@article{27614fbba9104b7d840246440f3aec1d,
title = "Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries",
abstract = "The “one-bead two-compound” (OB2C) combinatorial library is constructed on topologically segregated trifunctional bilayer beads such that each bead has a fixed cell-capturing ligand and a random library compound co-displayed on its surface and a chemical coding tag (bar code) inside the bead. An OB2C library containing thousands to millions of compounds can be synthesized and screened concurrently within a short period of time. When live cells are incubated with such OB2C libraries, every bead will be coated with a monolayer of cells. The cell membranes of the captured cells facing the bead surface are exposed to the library compounds tethered to each bead. A specific biochemical or cellular response can be detected with an appropriate reporter system. The OB2C method enables investigators to rapidly discover synthetic molecules that not only interact with cell-surface receptors but can also stimulate or inhibit downstream cell signaling. To demonstrate this powerful method, one OB2C peptide library and two OB2C peptidomimetic libraries were synthesized and screened against Molt-4 lymphoma cells to discover “death ligands.” Apoptosis of the bead-bound cells was detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated anti-cleaved caspase-3 antibody and 3,3′-diaminobenzidine as a substrate. Two novel synthetic “death ligands” against Molt-4 cells were discovered using this OB2C library approach.",
keywords = "Apoptosis, Bilayer bead, Cell-capturing ligand, Immunocytochemistry, Lymphoma, OB2C combinatorial library, Proapoptotic agent, Synthetic “death ligand”",
author = "Ruiwu Liu and Shih, {Tsung Chieh} and Xiaojun Deng and Lara Anwar and Sara Ahadi and Pappanaicken Kumaresan and Lam, {Kit S.}",
year = "2015",
doi = "10.1007/978-1-4939-2020-4_1",
language = "English (US)",
volume = "1248",
pages = "1--2",
journal = "Methods in molecular biology (Clifton, N.J.)",
issn = "1064-3745",
publisher = "Humana Press",

}

TY - JOUR

T1 - Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries

AU - Liu, Ruiwu

AU - Shih, Tsung Chieh

AU - Deng, Xiaojun

AU - Anwar, Lara

AU - Ahadi, Sara

AU - Kumaresan, Pappanaicken

AU - Lam, Kit S.

PY - 2015

Y1 - 2015

N2 - The “one-bead two-compound” (OB2C) combinatorial library is constructed on topologically segregated trifunctional bilayer beads such that each bead has a fixed cell-capturing ligand and a random library compound co-displayed on its surface and a chemical coding tag (bar code) inside the bead. An OB2C library containing thousands to millions of compounds can be synthesized and screened concurrently within a short period of time. When live cells are incubated with such OB2C libraries, every bead will be coated with a monolayer of cells. The cell membranes of the captured cells facing the bead surface are exposed to the library compounds tethered to each bead. A specific biochemical or cellular response can be detected with an appropriate reporter system. The OB2C method enables investigators to rapidly discover synthetic molecules that not only interact with cell-surface receptors but can also stimulate or inhibit downstream cell signaling. To demonstrate this powerful method, one OB2C peptide library and two OB2C peptidomimetic libraries were synthesized and screened against Molt-4 lymphoma cells to discover “death ligands.” Apoptosis of the bead-bound cells was detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated anti-cleaved caspase-3 antibody and 3,3′-diaminobenzidine as a substrate. Two novel synthetic “death ligands” against Molt-4 cells were discovered using this OB2C library approach.

AB - The “one-bead two-compound” (OB2C) combinatorial library is constructed on topologically segregated trifunctional bilayer beads such that each bead has a fixed cell-capturing ligand and a random library compound co-displayed on its surface and a chemical coding tag (bar code) inside the bead. An OB2C library containing thousands to millions of compounds can be synthesized and screened concurrently within a short period of time. When live cells are incubated with such OB2C libraries, every bead will be coated with a monolayer of cells. The cell membranes of the captured cells facing the bead surface are exposed to the library compounds tethered to each bead. A specific biochemical or cellular response can be detected with an appropriate reporter system. The OB2C method enables investigators to rapidly discover synthetic molecules that not only interact with cell-surface receptors but can also stimulate or inhibit downstream cell signaling. To demonstrate this powerful method, one OB2C peptide library and two OB2C peptidomimetic libraries were synthesized and screened against Molt-4 lymphoma cells to discover “death ligands.” Apoptosis of the bead-bound cells was detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated anti-cleaved caspase-3 antibody and 3,3′-diaminobenzidine as a substrate. Two novel synthetic “death ligands” against Molt-4 cells were discovered using this OB2C library approach.

KW - Apoptosis

KW - Bilayer bead

KW - Cell-capturing ligand

KW - Immunocytochemistry

KW - Lymphoma

KW - OB2C combinatorial library

KW - Proapoptotic agent

KW - Synthetic “death ligand”

UR - http://www.scopus.com/inward/record.url?scp=84922011527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922011527&partnerID=8YFLogxK

U2 - 10.1007/978-1-4939-2020-4_1

DO - 10.1007/978-1-4939-2020-4_1

M3 - Article

C2 - 25616322

AN - SCOPUS:84922011527

VL - 1248

SP - 1

EP - 2

JO - Methods in molecular biology (Clifton, N.J.)

JF - Methods in molecular biology (Clifton, N.J.)

SN - 1064-3745

ER -