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Stability and Conformational Analysis of Tc-RC160 and Re-RC160: Experimental and Theoretical Analysis of the Influence of Metal Complexation on the Structural Requisites for Activity
The biological significance of somatostatin and related synthetic peptide analogs is well documented. These peptide analogs have demonstrated inhibitory effects on the growth of certain tumor lines including prostate, breast, and pancreas. Metal−peptide analogs have been developed for imaging small...
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| Published in: | Journal of physical chemistry (1952) 1996-08, Vol.100 (35), p.14630-14636 |
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| Main Authors: | , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
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| Summary: | The biological significance of somatostatin and related synthetic peptide analogs is well documented. These peptide analogs have demonstrated inhibitory effects on the growth of certain tumor lines including prostate, breast, and pancreas. Metal−peptide analogs have been developed for imaging small tumors overexpressing somatostatin receptors, i.e. receptor-based scintigraphy. Receptor-based scintigraphy requires that the binding constant of the metal−peptide analog be competitive with that of the native somatostatin analog. For these applications an isotope of technetium, 99mTc is a particularly useful label. To address the effect of added label on the native peptide conformation and predicted impact on its efficacy as a therapeutic imaging agent, a combination of experimental and computational techniques were used. In this work, a complete analysis of an active Tc- or Re-labeled somatostatin analog is provided through comparison of optical, MS, and NMR data. Computational modeling has assisted in providing a profile of energetic preferences for the various coordination isomers. Coupled with optical spectral data this modeling also provides a description of the electronic states giving the characteristic bands in the optical spectra and helps to describe the redox activity and stability of the complex. On the basis of this information the structure of a major isomer is proposed. The analysis suggests that only certain coordination isomers will be accommodated by peptide without significant distortion of the “active” conformation. Furthermore, this work provides useful information for the rational design of labeled peptides with increased stability. |
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| ISSN: | 0022-3654 1541-5740 |
| DOI: | 10.1021/jp960024l |