Send to

Choose Destination
ChemistryOpen. 2019 Jun 7;8(6):737-742. doi: 10.1002/open.201900110. eCollection 2019 Jun.

Conjugates of Cryptophycin and RGD or isoDGR Peptidomimetics for Targeted Drug Delivery.

Author information

Organic and Bioorganic Chemistry, Department of Chemistry Bielefeld University Universitätsstraße 25 DE-33615 Bielefeld Germany.
Exiris s.r.l. Via di Castel Romano 100 IT-00128 Rome Italy.
Dipartimento di Scienza e Alta Tecnologia Università degli Studi dell'Insubria Via Valleggio, 11 IT-22100 Como Italy.
Dipartimento di Chimica Università degli Studi di Milano Via C. Golgi, 19 IT-20133 Milano Italy.
Istituto di Scienze e Tecnologie Molecolari (ISTM) CNR Via C. Golgi, 19 IT-20133 Milano Italy.


RGD-cryptophycin and isoDGR-cryptophycin conjugates were synthetized by combining peptidomimetic integrin ligands and cryptophycin, a highly potent tubulin-binding antimitotic agent across lysosomally cleavable Val-Ala or uncleavable linkers. The conjugates were able to effectively inhibit binding of biotinylated vitronectin to integrin αvβ3, showing a binding affinity in the same range as that of the free ligands. The antiproliferative activity of the novel conjugates was evaluated on human melanoma cells M21 and M21-L with different expression levels of integrin αvβ3, showing nanomolar potency of all four compounds against both cell lines. Conjugates containing uncleavable linker show reduced activity compared to the corresponding cleavable conjugates, indicating efficient intracellular drug release in the case of cryptophycin-based SMDCs. However, no significant correlation between the in vitro biological activity of the conjugates and the integrin αvβ3 expression level was observed, which is presumably due to a non-integrin-mediated uptake. This reveals the complexity of effective and selective αvβ3 integrin-mediated drug delivery.


antitumor agents; cancer; drug delivery; integrins; peptidomimetics

Conflict of interest statement

A.M. is an employee of Exiris, P.G. is a shareholder of Exiris. C.S. is a shareholder of Exiris.

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center