Rhenium-labeled somatostatin analog RC-160. 1H NMR and computer modeling conformational analysis.

Varnum, James M.; Thakur, Madhukar L; Schally, A. V.; Jansen, Susan A.; Mayo, Kevin H.

doi:10.1016/s0021-9258(18)99915-1

Cited by 25 publications

(11 citation statements)

References 21 publications

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“…The topology of the side chains of Trp4 and Lys5 are not affected by metal coordination. This is entirely consistent with the earlier NMR analysis (Varnum 1994).…”

Section: Identification Of the Re-rc160 Complex In Solutionsupporting

confidence: 92%

“…The cyclic somatostatin analog RC160, was synthesized using Merrifield solid phase methodology. The synthesis and purification procedures for the rhenium-labeled RC160 were reported elsewhere (Varnum 1994). The purity of the reaction product was analyzed by reverse phase HPLC.…”

Section: Methodsmentioning

confidence: 99%

“…Careful analysis of structures showed good agreement and reliability between the methods. The starting structures were previously determined by restrained molecular modeling (Varnum 1994). These structures were modified by adding a suitable octahedrally coordinated metal.…”

Section: Methodsmentioning

confidence: 99%

“…Characterization of Metal Complex Geometry. The solution structure of the RC160 complex has been discussed in detail elsewhere, and thus only the critical features of the structure will be described here (Varnum 1994). This structure was obtained by a combination of NMR and molecular modeling techniques, as described in the Experimental Section.…”

Section: Identification Of the Re-rc160 Complex In Solutionmentioning

confidence: 99%

“…This means that for this technique to be effective the radiolabel cannot significantly alter the important structural features of the peptide that determine receptor specificity or affinity, including steric, hydrophobic, and electrostatic interactions critical for binding. The structure of 99m Tc-labeled RC160 has been inferred using NMR and molecular modeling techniques on a related rhenium-labeled peptide, Re-RC160 peptide (Varnum 1994). This study has shown that backbone conformation and side-chain topology of the analogous rhenium-labeled peptide structure closely resemble the unlabeled form of the cyclic peptide.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 1996

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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, 99m Tc 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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“…The topology of the side chains of Trp4 and Lys5 are not affected by metal coordination. This is entirely consistent with the earlier NMR analysis (Varnum 1994).…”

Section: Identification Of the Re-rc160 Complex In Solutionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Identification Of the Re-rc160 Complex In Solutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations