Developing an efficient and general strategy for immobilization of small molecules onto microarrays using isocyanate chemistry

Chenggang Zhu, Xiangdong Zhu, James P. Landry, Zhaomeng Cui, Quanfu Li, Yongjun Dang, Lan Mi, Fengyun Zheng, Yiyan Fei

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%.

Original languageEnglish (US)
Article number378
JournalSensors (Switzerland)
Volume16
Issue number3
DOIs
StatePublished - Mar 16 2016

Fingerprint

Isocyanates
isocyanates
Microarrays
immobilization
Immobilization
chemistry
Molecules
molecules
platforms
Printing
Lead compounds
lead compounds
Drug Discovery
Carboxylic Acids
Glass
activity (biology)
Carboxylic acids
chutes
carboxylic acids
printing

Keywords

  • High-throughput screening
  • Label-free optical biosensor
  • Small-molecule microarrays
  • Surface functionalization

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Atomic and Molecular Physics, and Optics
  • Analytical Chemistry
  • Biochemistry

Cite this

Developing an efficient and general strategy for immobilization of small molecules onto microarrays using isocyanate chemistry. / Zhu, Chenggang; Zhu, Xiangdong; Landry, James P.; Cui, Zhaomeng; Li, Quanfu; Dang, Yongjun; Mi, Lan; Zheng, Fengyun; Fei, Yiyan.

In: Sensors (Switzerland), Vol. 16, No. 3, 378, 16.03.2016.

Research output: Contribution to journalArticle

Zhu, Chenggang ; Zhu, Xiangdong ; Landry, James P. ; Cui, Zhaomeng ; Li, Quanfu ; Dang, Yongjun ; Mi, Lan ; Zheng, Fengyun ; Fei, Yiyan. / Developing an efficient and general strategy for immobilization of small molecules onto microarrays using isocyanate chemistry. In: Sensors (Switzerland). 2016 ; Vol. 16, No. 3.
@article{acf60f2a93734832be05518e89ab5643,
title = "Developing an efficient and general strategy for immobilization of small molecules onto microarrays using isocyanate chemistry",
abstract = "Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73{\%}.",
keywords = "High-throughput screening, Label-free optical biosensor, Small-molecule microarrays, Surface functionalization",
author = "Chenggang Zhu and Xiangdong Zhu and Landry, {James P.} and Zhaomeng Cui and Quanfu Li and Yongjun Dang and Lan Mi and Fengyun Zheng and Yiyan Fei",
year = "2016",
month = "3",
day = "16",
doi = "10.3390/s16030378",
language = "English (US)",
volume = "16",
journal = "Sensors (Switzerland)",
issn = "1424-8220",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",

}

TY - JOUR

T1 - Developing an efficient and general strategy for immobilization of small molecules onto microarrays using isocyanate chemistry

AU - Zhu, Chenggang

AU - Zhu, Xiangdong

AU - Landry, James P.

AU - Cui, Zhaomeng

AU - Li, Quanfu

AU - Dang, Yongjun

AU - Mi, Lan

AU - Zheng, Fengyun

AU - Fei, Yiyan

PY - 2016/3/16

Y1 - 2016/3/16

N2 - Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%.

AB - Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%.

KW - High-throughput screening

KW - Label-free optical biosensor

KW - Small-molecule microarrays

KW - Surface functionalization

UR - http://www.scopus.com/inward/record.url?scp=84962573764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962573764&partnerID=8YFLogxK

U2 - 10.3390/s16030378

DO - 10.3390/s16030378

M3 - Article

VL - 16

JO - Sensors (Switzerland)

JF - Sensors (Switzerland)

SN - 1424-8220

IS - 3

M1 - 378

ER -