Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins

Abstract

Porcine leukocytes contained three homologous peptides, PG‐1, 2 and 3, that manifested potent microbicidal activity against Escherichia coli, Listeria monocytogenes and Candida albicans in vitro. The peptides (‘protegrins’) were composed of 16 (PG‐2) or 18 amino acid residues, and, like tachyplesins (broad‐spectrum antibiotic peptides of horseshoe crab hemocytes), they contained two intramolecular cystine disulfide bonds. Considerably smaller than defensins, protegrins nevertheless showed substantial homology to them, especially to the ‘corticostatic’ rabbit defensin, NP‐3a. The relatively simple structure of protegrins should provide useful prototypes for constructing congeners with selectively enhanced host defense activities.

Structure and dynamics of cationic membrane peptides and proteins: Insights from solid‐state NMR

“…It is derived from porcine leukocytes and has broadspectrum antimicrobial activities. 57,68,69 The structure-activity relation of PG-1 has been explored extensively. 70 13 C and 15 N chemical shifts confirmed the b-strand conformation of the peptide in lipid membranes 71,72 as in solution.…”

Cathelicidins: a novel protein family with a common proregion and a variable C‐terminal antimicrobial domain

“…Peptides corresponding to all known sequences have either been purified from natural sources [13,[34][35][36][37][38][39], after processing of the respective precursors, or have been obtained by chemical synthesis based on the sequence deduced from cDNA [26,27,29,32,33]. At present they include rabbit CAPI8(106 142) [39], human FALL-39/CAP18 [32,33], PMAP-36 [26] and PMAP-37 [29], all of which are mostly s-helical; two Trpcontaining peptides, indolicidin [36] and PMAP-23 [27]; the Pro-and Arg-rich Bac5 [12], Bac7 [12], PR-39 [13] and prophenin [38]; the cyclic dodecapeptide [34] and protegrins [37] which are loop-forming molecules with one and two disulfide bonds, respectively. The sequence of the Pro-and Arg-rich peptides (Fig.…”

“…The Pro-and Arg-rich peptides are substantially more active against gram-negative than gram-positive bacteria [13,35,38]. Conversely, the other linear (helical and Trp-rich) and Cys-containing peptides are in general highly active against both gram-positive and gramnegative microorganisms [26,27,32,34,36,37,49]. Protegrins also exhibit fungicidal activity [37], while Bac5 and Bac7 kill leptospirae [50].…”

Prophenin‐1, an exceptionally proline‐rich antimicrobial peptide from porcine leukocytes

“…Although these peptides show marked diversity in structure and antimicrobial spectrum, the precursors of many antibiotic peptides of porcine [2 6], bovine [7][8][9][10] and rabbit [11,12] origin contain a highly conserved preproregion that is homologous to cathelin, a putative cysteine-proteinase inhibitor originally isolated from pig leukocytes [13,14]. Several of these cathelin-associated peptides have been isolated and characterized, including porcine PR-39 [15] and protegrins PG-1, 2 and 3 [16]; bovine Bac 5 [17,18], indolicidin 9 [19] and cyclic dodecapeptide [20]; and rabbit p15 [12] and CAP 18 [11]. Others such as porcine PMAP-36 [5], PMAP-23 [6] and have been prepared for study by chemical synthesis based on sequence translations from cloned cDNA.…”