Solid phase synthetic methodology has been developed in our laboratory to incorporate an affinity label (a reactive functionality such as isothiocyanate or bromoacetamide) into peptides (Leelasvatanakij, L. and Aldrich, J. V. (2000) J. Peptide Res. 56, 80), and we have used this synthetic strategy to prepare affinity label derivatives of a variety of opioid peptides. To date side reactions have been detected only in two cases, both involving intramolecular cyclization. We have identified several peptide-based affinity labels for δ opioid receptors that exhibit wash-resistant inhibition of binding to these receptors and are valuable pharmacological tools to study opioid receptors. Even in cases where the peptide derivatives do not bind covalently to their target receptor, studying their binding has revealed subtle differences in receptor interactions with particular opioid peptide residues, especially Phe residues in the N-terminal "message" sequences. Solid phase synthetic methodology for the incorporation of other labels (e.g. biotin) into the C-terminus of peptides has also been developed in our laboratory (Kumar, V. and Aldrich, J. V. (2003) Org. Lett. 5, 613). These two synthetic approaches have been combined to prepare peptides containing multiple labels that can be used as tools to study peptide ligand-receptor interactions. These solid phase synthetic methodologies are versatile strategies that are applicable to the preparation of labeled peptides for a variety of targets in addition to opioid receptors.

The importance of the amorphous state in studying bioavailability of poorly water-soluble drugs cannot be over-emphasized. The higher free energy and therefore the apparent high solubility of the amorphous phase are some of the advantages for promoting the amorphous phase, as compared to its crystalline counterpart. It is well known that the amorphous phase is thermodynamically unstable. This might result in the conversion of the metastable form to its stable crystalline form during storage. This conversion might also lead to product failure during storage owing to the poor dissolution properties of the crystalline form. Excipients can play a key role in preventing such a transformation during storage as well as maximizing the therapeutic efficacy of the amorphous material. This book chapter intends to highlight the delivery issues pertaining to amorphous drugs with a special emphasis on the most commonly used excipients in stabilizing amorphous drug substances in formulations.

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Organic chemistry Z 0200 Solid-Phase Synthesis and Application of Labeled Peptide Derivatives: Probes of Receptor-Opioid Peptide Interactions -[41 refs.]. -(ALDRICH, J. V.; KUMAR, V.; DATTACHOWDHURY, B.; PECK, A. M.; WANG, X.; MURRAY, T. F.; Int. J.