@article {44116,
	title = {Overcoming the lack of oral availability of cyclic hexapeptides: design of a selective and orally available ligand for the integrin alpha v beta 3},
	journal = {Angewandte Chemie-International Edition},
	volume = {56},
	year = {2017},
	month = {DEC},
	pages = {16405-16409},
	type = {Article},
	abstract = {Ahighly systematic approach for the development of both orally bioavailable and bioactive cyclic N-methylated hexapeptides as high affinity ligands for the integrin alpha v beta 3 is based on two concepts: a) screening of systematically designed libraries with spatial diversity and b) masking of the peptide charge with a lipophilic protecting group. The key steps of the method are 1) initial design of a combinatorial library of Nmethylated analogues of the stem peptide cyclo(d-Ala-Ala(5)); 2) selection of cyclic peptides with the highest intestinal permeability; 3) design of sublibraries with the bioactive RGD sequence in all possible positions; 4) selection of the best ligands for RGD-recognizing integrin subtypes; 5) finetuning of the affinity and selectivity by additional Ala to Xaa substitutions; 6) protection of the charged functional groups according to the prodrug concept to regain intestinal and oral permeability; 7) proof of biological effects in mice after oral administration.},
	doi = {10.1002/anie.201709709},
	author = {Weinmueller, Michael and Rechenmacher, Florian and Marelli, Udaya Kiran and Reichart, Florian and Kapp, Tobias G. and Raeder, Andreas F. B. and Di Leva, Francesco Saverio and Marinelli, Luciana and Novellino, Ettore and Munoz-Felix, Jose M. and Hodivala-Dilke, Kairbaan and Schumacher, Adi and Fanous, Joseph and Gilon, Chaim and Hoffman, Amnon and Kessler, Horst}
}
@article {45401,
	title = {From a helix to a small cycle: metadynamics-inspired alpha v beta 6 integrin selective ligands},
	journal = {Angewandte Chemie-International Edition},
	volume = {57},
	year = {2018},
	month = {OCT},
	pages = {14645-14649},
	type = {Article},
	abstract = {The RGD-recognizing alpha v beta 6 integrin has only recently emerged as a major target for cancer diagnosis and therapy. Thus, the development of selective, low-molecular-weight ligands of this receptor is still in great demand. Here, a metadynamics-driven design strategy allowed us to successfully convert a helical nonapeptide into a cyclic pentapeptide (6) showing remarkable potency and alpha v beta 6 specificity. NMR and docking studies elucidated the reasons for the high affinity and selectivity of this compound, setting the ground for the rational design of new alpha v beta 6-specific small peptides or even peptidomimetics. In vivo PET imaging studies demonstrated the potential use of 6 for medical applications.},
	issn = { 1433-7851},
	doi = {10.1002/anie.201803250},
	author = {Di Leva, Francesco Saverio and Tomassi, Stefano and Di Maro, Salvatore and Reichart, Florian and Notni, Johannes and Dangi, Abha and Marelli, Udaya Kiran and Brancaccio, Diego and Merlino, Francesco and Wester, Hans-Juergen and Novellino, Ettore and Kessler, Horst and Marinelli, Luciana}
}
@article {44597,
	title = {N-Methylation of isoDGR peptides: discovery of a selective alpha 5 beta 1-integrin ligand as a potent tumor imaging agent},
	journal = {Journal of Medicinal Chemistry},
	volume = {61},
	year = {2018},
	month = {MAR},
	pages = {2490-2499},
	type = {Article},
	abstract = {<p>Specific targeting of the integrin subtype alpha 5 beta 1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective alpha 5 beta 1/alpha v beta 6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding aSfil subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg-isoDGR-(NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring alpha 5 beta 1 integrin expression in a M21 mouse xenograft.</p>},
	issn = {0022-2623},
	doi = {10.1021/acs.jmedchem.7b01752},
	author = {Kapp, Tobias G. and Di Leva, Francesco Saverio and Notni, Johannes and Raeder, Andreas F. B. and Fottner, Maximilian and Reichart, Florian and Reich, Dominik and Wurzer, Alexander and Steiger, Katja and Novellino, Ettore and Marelli, Udaya Kiran and Wester, Hans-Juergen and Marinelli, Luciana and Kessler, Horst}
}
