Peptidic Macrocycles
    Peptidomimetic compound libraries play a pivotal role in the discovery ofnew molecules with high activity, specificity, and affinity against many therapeutically relevant targets. Synthetic analogs of natural peptides can effectively mimic the structural elements of natural ligands and produce the desired biological effect but further efforts are required to address metabolic challenges such as resistance to peptidases and permeability. Several studies suggest that the macrocyclization of peptidomimetics is an attractive strategy to improve important biological properties. Macrocyclic peptidomimetic compound libraries would, therefore,be a useful starting point in drug discovery. ASINEX has been continuously improving the design of macrocyclic compounds that can effectively mimic biologically relevant di- and tripeptide motifs which can serve as topological mimics of the secondary structuresof peptides (e.g.: alpha helixes, beta turns). Our approach is based on the synthesis of conformationally constrained, macrocyclic cores that typically contain 2-4 cyclic amide groups, along with several additional points of diversity which are used for the introduction of lipophilic or hydrophilic side chains. At ASINEX, the synthesis of macrocyclic compounds was carried out using two fundamental strategies: a macrolactamization approach of an amino acid precursor and a ring-closing metathesis (RCM) of a bis-olefin precursors. Our peptidic macrocycles tend to be larger than our scaffold-based non-peptidic macrocycles, yet many compounds demonstrate favorable aqueous solubility and membrane permeability as measured by PAMPA and Caco-2 assays.
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Ludmila Sadovenko
lsadovenko@asinex.comMark Parisi
mparisi@asinex.comToll Free: +1 877 ASINEX1
Tel: +1 336 721 1617
Fax: +1 336 721 1618
N.Chestnut St., Ste.104
Winston-Salem, NC 27101
USA
Ludmila Sadovenko
lsadovenko@asinex.comGalina Afanasyeva
gafanasyeva@asinex.comTel: +31 (0) 203416183
Klaprozenweg 75C, 1033NN
Amsterdam, The Netherlands