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Pharmaceutical Regulatory Affairs: Open Access

ISSN: 2167-7689

Open Access

Amide-based Disulfide Building Blocks for the Enlargement of the Solid Phase Peptide Synthesis for Molecular Diagnostics and Imaging

Abstract

Braun K, Wiessler M, Komljenovic D, Schrenk HH, Lorenz P, Fleischhacker H, Waldeck W and Pipkorn R

Progress in genome and proteome research led to a deeper insight in differential gene expression processes. This required the use of sensitive and specific tools in diagnostics; also new promising patient-specific therapy attempts are conceivable. Nucleic acids were up till now a critical goal for diagnostic applications and therapeutic interventions, but in future they can serve as highly sequence-specific tools in molecular diagnostics. Examples for diagnostic Molecular Imaging modalities are the analysis of metabolic processes which can lead to customized therapeutic approaches (“Targeted Therapy”). The solid phase peptide synthesis SPPS is considered as an excellent tool in the individualized medicine with nucleic acids which increasingly play a key role as a drug. This requires new properties of the nucleic acid-based drugs, contiguous to the stability in biological systems, a high variability by combination with functional peptide-based molecules or with reformulated drugs or imaging components. The multifaceted application spectrum is dependent on the patients’ individual differential gene expression profiles or on the medical questionnaire. Here we show a new synthesis strategy able to circumvent ligations steps and to enhance the yields in the SPPS technology by use of a novel disulfide-containing monomer. This molecule acts as a disulfide linker which can overcome the common occasional losses occurring during established coupling reactions, like disulfide-bridge formations.

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Citations: 533

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