Crotamine and crotalicidin, membrane active peptides from Crotalus durissus terrificus rattlesnake venom, and their structurally-minimized fragments for applications in medicine and biotechnology

Cell-Penetrating Peptides Derived from Animal Venoms and Toxins

“…Vipericidins, in general and crotalicidin, in particular, are surprisingly similar to previously characterized Asian elapid CRAMPs, despite South American pit vipers and Asian elapids (cobras and kraits) being geographically and phylogenetically distant venomous snake groups, which evolutionarily diverged millions of years ago. Multiple biological activities have been reported for crotalicidin, vipericidin-related sequences and elapid CRAMPs, with emphasis on antipathogenic and antitumoral properties, as reviewed elsewhere [135,[155][156][157]. The antimicrobial activity ranges from multidrug-resistant clinical isolates to life-threatening viruses, as reported for cathelicidin-OH30 derived from the venom of the king cobra Ophiophagus hannah, as well as venom cathelicidin-BF30 and short derivatives from the banded krait Bungarus fasciatus venom [158,159].…”

“…The cell penetration property of crotamine, in addition to its antiproliferative activity and other functionalities, has been reviewed in several articles recently published [135], as well as in the last decade [136][137][138]. The penetrability of crotamine was observed with fluorescent cyanine 3-labeled native peptide and diverse cell types in culture, including mouse blastocysts and embryonic stem cells [139].…”

Antibiofilm Activity on Candida albicans and Mechanism of Action on Biomembrane Models of the Antimicrobial Peptide Ctn[15–34]

“…The development of new antimicrobial drugs remains a major challenge to overcome the spread of drug resistance of clinically-relevant microbes, as strains are increasingly becoming less sensitive to conventional antibiotics. Previous studies have demonstrated that the crotalicidin fragment Ctn [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] is an effective antimicrobial peptide, with distinct anti-infective and anti-proliferative activities [13,14]. Its physicochemical properties, including small size, positive net charge, high hydrophobicity, and intermediate hydrophobic moment, endow Ctn [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] with a well-balanced structure-activity profile that makes it biologically active against bacteria and certain tumor cells, as well as stable in biological fluids [15,16].…”

“…Ctn (KRFKKFFKKVKKSVKKRLKKIFKKPMVIGVTIPF), Ctn [1][2][3][4][5][6][7][8][9][10][11][12][13][14] (KRFKKFFKKVKKSV), and Ctn [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] (KKRLKKIFKKPMVIGVTIPF) were synthesized by solid phase methods, purified by HPLC to >95% homogeneity, and characterized by ESI-mass spectrometry, as previously described Figure 6. Depicted mechanism of action of Ctn [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]…”

“…Ctn (KRFKKFFKKVKKSVKKRLKKIFKKPMVIGVTIPF), Ctn[1-14] (KRFKKFFKKVKKSV), and Ctn [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] (KKRLKKIFKKPMVIGVTIPF) were synthesized by solid phase methods, purified by HPLC to >95% homogeneity, and characterized by ESI-mass spectrometry, as previously described [13]. Peptide stock solutions (1 mM) were prepared in sterile Milli-Q water and stored in aliquots at −20 • C, until use.…”