Naslov
Host defense peptides as natural product scaffolds for a design of next generation antibiotic classes

Autori
Juretić, Davor

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Proceedings of the First Adriatic Symposium on Biophysical Approaches in Biomedical Studies / Raguž, Marija ; Kalyanaraman, Balaraman ; Sarna, Tadeusz ; Ilić, Nada ; Nejašmić, Danijel ; Thelaner, Jane - Split : Mediterranean Institute for Life Sciences (MedILS), 2014, 53-53

ISBN
978-953-55188-2-2

Skup
First Adriatic Symposium on Biophysical Approaches in Biomedical Studies

Mjesto i datum
Split, Hrvatska, 24.08.2014. - 29.08.2014

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
bacterial resistance; host defense peptides; peptide antibiotics; therapeutic index; computational design; web server

Sažetak
An alarming drop in discoveries of new antibiotic scaffolds has occurred during last forty years, precisely at the time of accelerated development and worldwide spread of bacterial resistance. Host defense peptides (HDP) have all of desired drug attributes: fast acting (often with broad spectrum activity), low spontaneous resistance rates, amenability to generations of chemical tailoring and no cross-resistance to existing antibiotics. Synthetic peptides derived from HDF have been shown to exhibit synergistic or additive effects when combined with classical antibiotics. We took care to improve what has been lacking for HDF of non-human origin: a rational means (algorithms) for decreasing their toxicity to human cells and increasing their selectivity against bacterial cells. During last several years this effort resulted in finding dozen peptide antibiotics with high therapeutic index, such as adepantins, ascaphin-8 and XT-7 double substitution analogues, hfp1 and its analogues, trichoplaxin and kiadin, all designed by using evolutionary information stored in frog, fish and placozoa antimicrobial peptides. With completely different primary structure, these peptides pose biophysical challenge to find specificity/selectivity determinants from their membrane-associated 3D structure. To facilitate additional discoveries, we provide free for use on-line web server for in silico design of potential peptide antibiotics: http://split4.pmfst.hr/mutator/.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

POVEZANOST RADA