Melusine's unique hit-to-lead deconvolution strategy

Once bioactivity is identified in a well of a Melusine library, based on our standard procedures and making best use of our proprietary biocomputing platform and databases, we typically undertake the following deconvolution and lead optimization strategy:

• Analysis of bioactive wells by mass spectrometry (MS & MS/MS), evaluation & selection of best wells;
• Resupply on a “per-well” basis is proposed if required for bioassays;
• Sub-fractionation of selected wells and delivery of sub-fractions for bioassays;
• Analysis of active sub-fractions by mass spectrometry, evaluation & selection of best sub-fraction;
• Scale-up preparation of selected sub-fractions to pursue the deconvolution process;
• Second sub-fractionation step, delivery of isolated biomolecules for bioassays;
• Analysis of active biomolecules by mass spectrometry, evaluation & selection of best candidates;
• Amino acid sequencing of purified hits by automated Edman chemistry, evaluation;
• In depth structural elucidation using protein microtechniques, MS and de novo MS/MS sequencing;
• Homology searches with extensive data- and text-mining strategies, evaluation and hit selection;
• Solid phase peptide synthesis of best hits, delivery for in depth bioassays and various investigations;
• Technology survey and lead selection based on a range of stringent criteria.
• Lead optimization: screening for natural analogues (“wet-lab”) and in silico drug design (“dry-lab”).