### Abstract

A number of NMR methods possess the capability of probing chemical exchange dynamics in solution. However, certain drawbacks limit the applications of these NMR approaches, particularly, to a complex system. Here, we propose a procedure that integrates the regularized nonnegative least squares (NNLS) analysis of multiexponential T_{2} relaxation into Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments to probe chemical exchange in a multicompartmental system. The proposed procedure was validated through analysis of ^{19}F T_{2} relaxation data of 6-fluoro-DL-tryptophan in a two-compartment solution with and without bovine serum albumin. Given the regularized NNLS analysis of a T_{2} relaxation curve acquired, for example, at the CPMG frequency υ _{CPMG} = 125, the nature of two distinct peaks in the associated T_{2} distribution spectrum indicated 6-fluoro-DL-tryptophan either retaining the free state, with geometric mean/∗multiplicative standard deviation (MSD) = 1851.2 ms/1.51, or undergoing free/albumin-bound interconversion, with geometric mean/∗MSD = 236.8 ms∗/1.54, in the two-compartment system. Quantities of the individual tryptophan species were accurately reflected by the associated T_{2} peak areas, with an interconversion state-to-free state ratio of 0.45 ± 0.11. Furthermore, the CPMG relaxation dispersion analysis estimated the exchange rate between the free and albumin-bound states in this fluorinated tryptophan analog and the corresponding dissociation constant of the fluorinated tryptophan-albumin complex in the chemical-exchanging, two-compartment system.

Original language | English (US) |
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Pages (from-to) | 121-127 |

Number of pages | 7 |

Journal | Journal of Biomolecular NMR |

Volume | 62 |

Issue number | 2 |

DOIs | |

State | Published - Jun 4 2015 |

Externally published | Yes |

### Fingerprint

### Keywords

- Complex system
- Kinetics
- Multiexponential
- Nonnegative least squares analysis
- Protein-ligand interaction

### ASJC Scopus subject areas

- Biochemistry
- Spectroscopy

### Cite this

**Assessment of chemical exchange in tryptophan-albumin solution through ^{19}F multicomponent transverse relaxation dispersion analysis.** / Lin, Ping-Chang.

Research output: Contribution to journal › Article

}

TY - JOUR

T1 - Assessment of chemical exchange in tryptophan-albumin solution through 19F multicomponent transverse relaxation dispersion analysis

AU - Lin, Ping-Chang

PY - 2015/6/4

Y1 - 2015/6/4

N2 - A number of NMR methods possess the capability of probing chemical exchange dynamics in solution. However, certain drawbacks limit the applications of these NMR approaches, particularly, to a complex system. Here, we propose a procedure that integrates the regularized nonnegative least squares (NNLS) analysis of multiexponential T2 relaxation into Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments to probe chemical exchange in a multicompartmental system. The proposed procedure was validated through analysis of 19F T2 relaxation data of 6-fluoro-DL-tryptophan in a two-compartment solution with and without bovine serum albumin. Given the regularized NNLS analysis of a T2 relaxation curve acquired, for example, at the CPMG frequency υ CPMG = 125, the nature of two distinct peaks in the associated T2 distribution spectrum indicated 6-fluoro-DL-tryptophan either retaining the free state, with geometric mean/∗multiplicative standard deviation (MSD) = 1851.2 ms/1.51, or undergoing free/albumin-bound interconversion, with geometric mean/∗MSD = 236.8 ms∗/1.54, in the two-compartment system. Quantities of the individual tryptophan species were accurately reflected by the associated T2 peak areas, with an interconversion state-to-free state ratio of 0.45 ± 0.11. Furthermore, the CPMG relaxation dispersion analysis estimated the exchange rate between the free and albumin-bound states in this fluorinated tryptophan analog and the corresponding dissociation constant of the fluorinated tryptophan-albumin complex in the chemical-exchanging, two-compartment system.

AB - A number of NMR methods possess the capability of probing chemical exchange dynamics in solution. However, certain drawbacks limit the applications of these NMR approaches, particularly, to a complex system. Here, we propose a procedure that integrates the regularized nonnegative least squares (NNLS) analysis of multiexponential T2 relaxation into Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments to probe chemical exchange in a multicompartmental system. The proposed procedure was validated through analysis of 19F T2 relaxation data of 6-fluoro-DL-tryptophan in a two-compartment solution with and without bovine serum albumin. Given the regularized NNLS analysis of a T2 relaxation curve acquired, for example, at the CPMG frequency υ CPMG = 125, the nature of two distinct peaks in the associated T2 distribution spectrum indicated 6-fluoro-DL-tryptophan either retaining the free state, with geometric mean/∗multiplicative standard deviation (MSD) = 1851.2 ms/1.51, or undergoing free/albumin-bound interconversion, with geometric mean/∗MSD = 236.8 ms∗/1.54, in the two-compartment system. Quantities of the individual tryptophan species were accurately reflected by the associated T2 peak areas, with an interconversion state-to-free state ratio of 0.45 ± 0.11. Furthermore, the CPMG relaxation dispersion analysis estimated the exchange rate between the free and albumin-bound states in this fluorinated tryptophan analog and the corresponding dissociation constant of the fluorinated tryptophan-albumin complex in the chemical-exchanging, two-compartment system.

KW - Complex system

KW - Kinetics

KW - Multiexponential

KW - Nonnegative least squares analysis

KW - Protein-ligand interaction

UR - http://www.scopus.com/inward/record.url?scp=84930380027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930380027&partnerID=8YFLogxK

U2 - 10.1007/s10858-015-9929-4

DO - 10.1007/s10858-015-9929-4

M3 - Article

VL - 62

SP - 121

EP - 127

JO - Journal of Biomolecular NMR

JF - Journal of Biomolecular NMR

SN - 0925-2738

IS - 2

ER -