Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn

Aleksandra Baranczak, Stephen Connelly, Yu Liu, Sungwook Choi, Neil P. Grimster, Evan T. Powers, Ian A. Wilson, Jeffery W. Kelly

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We seek fluorogenic small molecules that generate a fluorescent conjugate signal if and only if they react with a given protein-of-interest (i.e., small molecules for which noncovalent binding to the protein-of-interest is insufficient to generate fluorescence). Consequently, it is the new chemical entity afforded by the generally irreversible reaction between the small molecule and the protein-of-interest that enables the energy of an electron occupying the lowest unoccupied molecular orbital (LUMO) of the chromophore to be given off as a photon instead of being dissipated by nonradiative mechanisms in complex biological environments. This category of fluorogenic small molecules is created by starting with environmentally sensitive fluorophores that are modified by an essential functional group that efficiently quenches the fluorescence until a chemoselective reaction between that functional group and the protein-of-interest occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are envisioned to be useful for a wide variety of applications, including live cell imaging without the requirement for washing steps and pulse-chase kinetic analyses of protein synthesis, trafficking, degradation, etc.

Original languageEnglish (US)
Pages (from-to)484-495
Number of pages12
JournalBiopolymers
Volume101
Issue number5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Proteins
Imaging techniques
Molecules
Fluorescence
Public Opinion
Functional groups
Protein Transport
Photons
Carrier Proteins
Electrons
Fluorophores
Molecular orbitals
Chromophores
Washing
Degradation
Kinetics

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

Cite this

Baranczak, Aleksandra ; Connelly, Stephen ; Liu, Yu ; Choi, Sungwook ; Grimster, Neil P. ; Powers, Evan T. ; Wilson, Ian A. ; Kelly, Jeffery W. / Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn. In: Biopolymers. 2014 ; Vol. 101, No. 5. pp. 484-495.
@article{dfe3c226c2c441febc0ea6b891fa1824,
title = "Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn",
abstract = "We seek fluorogenic small molecules that generate a fluorescent conjugate signal if and only if they react with a given protein-of-interest (i.e., small molecules for which noncovalent binding to the protein-of-interest is insufficient to generate fluorescence). Consequently, it is the new chemical entity afforded by the generally irreversible reaction between the small molecule and the protein-of-interest that enables the energy of an electron occupying the lowest unoccupied molecular orbital (LUMO) of the chromophore to be given off as a photon instead of being dissipated by nonradiative mechanisms in complex biological environments. This category of fluorogenic small molecules is created by starting with environmentally sensitive fluorophores that are modified by an essential functional group that efficiently quenches the fluorescence until a chemoselective reaction between that functional group and the protein-of-interest occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are envisioned to be useful for a wide variety of applications, including live cell imaging without the requirement for washing steps and pulse-chase kinetic analyses of protein synthesis, trafficking, degradation, etc.",
author = "Aleksandra Baranczak and Stephen Connelly and Yu Liu and Sungwook Choi and Grimster, {Neil P.} and Powers, {Evan T.} and Wilson, {Ian A.} and Kelly, {Jeffery W.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1002/bip.22407",
language = "English (US)",
volume = "101",
pages = "484--495",
journal = "Biopolymers",
issn = "0006-3525",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn. / Baranczak, Aleksandra; Connelly, Stephen; Liu, Yu; Choi, Sungwook; Grimster, Neil P.; Powers, Evan T.; Wilson, Ian A.; Kelly, Jeffery W.

In: Biopolymers, Vol. 101, No. 5, 01.01.2014, p. 484-495.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging-what we know and what we need to learn

AU - Baranczak, Aleksandra

AU - Connelly, Stephen

AU - Liu, Yu

AU - Choi, Sungwook

AU - Grimster, Neil P.

AU - Powers, Evan T.

AU - Wilson, Ian A.

AU - Kelly, Jeffery W.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - We seek fluorogenic small molecules that generate a fluorescent conjugate signal if and only if they react with a given protein-of-interest (i.e., small molecules for which noncovalent binding to the protein-of-interest is insufficient to generate fluorescence). Consequently, it is the new chemical entity afforded by the generally irreversible reaction between the small molecule and the protein-of-interest that enables the energy of an electron occupying the lowest unoccupied molecular orbital (LUMO) of the chromophore to be given off as a photon instead of being dissipated by nonradiative mechanisms in complex biological environments. This category of fluorogenic small molecules is created by starting with environmentally sensitive fluorophores that are modified by an essential functional group that efficiently quenches the fluorescence until a chemoselective reaction between that functional group and the protein-of-interest occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are envisioned to be useful for a wide variety of applications, including live cell imaging without the requirement for washing steps and pulse-chase kinetic analyses of protein synthesis, trafficking, degradation, etc.

AB - We seek fluorogenic small molecules that generate a fluorescent conjugate signal if and only if they react with a given protein-of-interest (i.e., small molecules for which noncovalent binding to the protein-of-interest is insufficient to generate fluorescence). Consequently, it is the new chemical entity afforded by the generally irreversible reaction between the small molecule and the protein-of-interest that enables the energy of an electron occupying the lowest unoccupied molecular orbital (LUMO) of the chromophore to be given off as a photon instead of being dissipated by nonradiative mechanisms in complex biological environments. This category of fluorogenic small molecules is created by starting with environmentally sensitive fluorophores that are modified by an essential functional group that efficiently quenches the fluorescence until a chemoselective reaction between that functional group and the protein-of-interest occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are envisioned to be useful for a wide variety of applications, including live cell imaging without the requirement for washing steps and pulse-chase kinetic analyses of protein synthesis, trafficking, degradation, etc.

UR - http://www.scopus.com/inward/record.url?scp=84896726947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896726947&partnerID=8YFLogxK

U2 - 10.1002/bip.22407

DO - 10.1002/bip.22407

M3 - Article

C2 - 24105107

AN - SCOPUS:84896726947

VL - 101

SP - 484

EP - 495

JO - Biopolymers

JF - Biopolymers

SN - 0006-3525

IS - 5

ER -