Spectroscopic and Calorimetric Approach to Understand the Molecular Basis of Self-Association of Aureolic Acid Antibiotic, Chromomycin A3

Shreyasi Dutta; Shibojyoti Lahiri; Dipak Dasgupta

doi:10.4236/ojbiphy.2014.42008

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Spectroscopic and Calorimetric Approach to Understand the Molecular Basis of Self-Association of Aureolic Acid Antibiotic, Chromomycin A3

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DOI: 10.4236/ojbiphy.2014.42008 3,020 Downloads 4,985 Views

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Shreyasi Dutta, Shibojyoti Lahiri, Dipak Dasgupta

Affiliation(s)

Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India.

ABSTRACT

Chromomycin A3 (CHR, pK_a = 7.0), an aureolic acid group of antitumor antibiotic, undergoes self-association in aqueous solution in neutral and anionic forms. Self-association processes of neutral and anionic CHR have been studied in pH 5.0 and pH 9.0, respectively using different spectroscopic methods such as absorbance, fluorescence, CD, NMR and isothermal titration calorimetry (ITC). Results from these studies reveal that at low concentration (<10 μM), CHR exists predominantly in dimeric state for both neutral and anionic forms. With the increase of concentration, dimers further aggregate to form trimer and teramer in the following steps: (CHR)₂ + CHR

(CHR)₃ and (CHR)₃ + CHR

(CHR)₄. Analysis of NMR spectra of 100 μM and 1 mM CHR indicates that the self-association of CHR (neutral and anionic form) is most likely to happen via hydrophobic interaction involving the sugar moieties and surrounding water molecules. Calorimetric studies indicate that self-association of both anionic and neutral CHR is entropy driven. These observations imply that sugar substituents play a major role in their state of aggregation after biosynthesis from a gene cluster. The self-association features of the antibiotic have been compared with those of Mithramycin, an antibiotic of the same group.

KEYWORDS

Oligomer; Neutral; Anionic; Circular Dichroism; Enthalpy; NMR Spectroscopy

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Dutta, S. , Lahiri, S. and Dasgupta, D. (2014) Spectroscopic and Calorimetric Approach to Understand the Molecular Basis of Self-Association of Aureolic Acid Antibiotic, Chromomycin A3. Open Journal of Biophysics, 4, 66-82. doi: 10.4236/ojbiphy.2014.42008.

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