Two‐dimensional proton‐NMR studies on a hybrid peptide between cecropin A and melittin

Sipos, David; Chandrasekhar, K; Arvidsson, Klas; Engström, Åke; Ehrenberg, Anders

doi:10.1111/j.1432-1033.1991.tb16122.x

Cited by 35 publications

(14 citation statements)

References 28 publications

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“…4). This assumption that the active cecropins and hybrids are amphipathic helices is well supported by data from several laboratories (16,(24)(25)(26). The parent peptide will be all-L and a right-handed helix.…”

Section: Resultssupporting

confidence: 55%

Retro and retroenantio analogs of cecropin-melittin hybrids

Bomani¹

1995

Peptides

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Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized. To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH' end groups, but acetylation restored activity against one of them. From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L-or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or, the direction of the peptide bonds could be critical but not both at the same time. For some strains, both needed to be conserved.Antimicrobial peptides have received increasing attention in recent years as their contribution to host defense mechanisms in the animal kingdom is gradually becoming appreciated. Several families of peptide antibiotics from animal sources have now been identified, including the cecropins from insects (1) and pigs (2), the defensins from neutrophils (3), melittin from the honey bee (4), and the magainins from frog skin (5) (for a recent review, see ref. 6). These peptides exhibit broad antibiotic responses against bacteria, protozoa, fungi, and viruses. The mature peptides, derived by the processing of larger precursors, have considerable sequence diversity but share common structural features, including a high content of basic amino acid residues and a global distribution of hydrophobic and hydrophilic residues leading to amphipathic a-helical conformations under hydrophobic conditions. Ion channel formation in artificial membranes has been described for cecropins (7), defensins (8), and magainins (9).Recent efforts have been directed toward a more detailed understanding of the mechanisms of action of the cecropins and their derivatives through the chemical synthesis of selected analogs. We found that certain 15-to 26-residue hybrids of segments of cecropins combined with segments of other antibacterial peptides, such as melittin, could lead to even more active peptides (10-12) and without introducing the inherent lytic properties of melittin toward eucaryotic cells. It was found that the enantiomers of several of these hybrids, composed of all D-amino acid residues, were fully active against all of our test bacterial strains (13,14). These results showed that the peptides do not function by chiral interactions with receptors, enzymes, or lipids. In the presence of a hydrophobicThe publication costs of this artic...

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Section: Resultssupporting

confidence: 55%

Retro and retroenantio analogs of cecropin-melittin hybrids

Bomani¹

1995

Peptides

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“…In addition, cecropin P1 has a more narrow antibacterial spectrum. The structures of cecropin A and a hybrid of cecropin A and mellitin in solution have been determined by Holak et al [20] and Sipos et al [25]. More recently, the conformation of the mammalian cecropin P1 has been studied by two-dimensional NOE spectroscopy (NOESY) [21].…”

Section: Structural Properties Of Secretolytinmentioning

confidence: 99%

Antibacterial activity of secretolytin, a chromogranin B‐derived peptide (614–626), is correlated with peptide structure

et al. 1996

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Amongst the chromogranin B (CGB) derived fragments naturally generated in bovine chromaffin granules and detected in the extracellular space, we recently identified a major peptide corresponding to the 614--626 sequence of CGB. This peptide, named secretolytin, shared an interesting sequence homology with the lyric domain of cecropins and displayed a potent antibacterial activity. The aim of the present study was to determine the structural features of secretolytin necessary for this biological activity. Our results suggest that an a-helical amphipathic structure common to secretolytin, cecropins and pig myeloid antibacterial peptide may account for the antibacterial activity.

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“…A cecropin has also been found in porcine small intestine . Insect cecropins are composed of two different domains linked by a hinge region (Holak et al, 1988), while the porcine cecropin is an extended helix with a flexible segment (Sipos et al, 1992). Melittin is a bee venom toxin that can form dimers.…”

Section: The Peptides Usedmentioning

confidence: 99%

“…The hybrid molecule CA( 1 -13) -melittin( 1 -13)-NH, with one domain from cecropin A [CA(l-13)] and another from melittin [melittin(l-13)] is a potent antibacterial and antimalarial agent (Boman et al, 1989b). The solution stucture is also known for this peptide (Sipos et al, 1991). Magainin 2 is an antimicrobial peptide from the skin of Xenopus luevis (Zasloff, 1987) and PR-39 is a proline-arginine rich antibacterial peptide from pig small intestine (Agerberth et al, 1991).…”

Section: The Peptides Usedmentioning

confidence: 99%

Antibacterial peptides and mitochonrial presequences affect mitochonrial coupling, respiration and protein import

Hugosson

Andreu

Boman

et al. 1994

European Journal of Biochemistry

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Cecropins A and P1, antibacterial peptides from insects and from pig and some related peptides released respiratory control, inhibited protein import and at higher concentrations also inhibited respiration. However, PR-39, an antibacterial peptide from pig intestine, was found to be almost inert towards mitochondria. The concentrations at which the three mitochondrial functions were effected varied for different peptides. Melittin, magainin and Cecropin-A-(1,13) -Melittin(l,l3)-NH2, a hybrid between cecropin A and melittin, were most potent, while the two cecropins acted at higher concentrations. The biosynthesis of cecropin A is known and the intermediates are synthesized. We have used four peptides from this pathway to investigate their effects on coupling, respiration and protein import into mitochondria. Mature cecropin A followed by the preproprotein were most aggressive whereas the intermediates were less active or inert. The efficiency of different derivatives of cecropin A as uncouplers correlates well with their capacity to release membrane potential measured as fluorescence quenching of Rhodamine 123. Inhibition of respiration was found to be dependent on membrane potential and was most pronounced with mature cecropin A, less so with its three precursors. We also found that three peptides derived from mitochondrial presequences showed antibacterial activity. It is concluded that, there are similarities in the functions of antibacterial peptides and mitochondrial presequences, uncoupling activity in mitochondria cannot be correlated with the antibacterial activity (contrary to a previous suggestion), the processing of preprocecropin A may have evolved in such a way that there is a minimum of membrane damage from the intermediates in the pathway, and peptides produced for delivery outside of an animal have evolved to be more aggressive against mitochondria than peptides for delivery inside of the animal.During the last 13 years several classes of broadspectrum antibacterial peptides have been discovered in the animal kingdom, among them cecropins, defensins and magainins (reviewed by Boman, 1991 ;Zasloff, 1992). These three groups of peptides are well characterized, they have been cloned, their three-dimensional structures are known and for cecropins and defensins the gene structures have been determined. All three groups of peptides also form channels in artificial membranes but it is not yet known if channel formation is responsible for the lethal activity on bacteria. There are clear structural similarities between certain antiCorrespondence to E. Glaser,

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Two‐dimensional proton‐NMR studies on a hybrid peptide between cecropin A and melittin

Cited by 35 publications

References 28 publications

Retro and retroenantio analogs of cecropin-melittin hybrids

Retro and retroenantio analogs of cecropin-melittin hybrids

Antibacterial activity of secretolytin, a chromogranin B‐derived peptide (614–626), is correlated with peptide structure

Antibacterial peptides and mitochonrial presequences affect mitochonrial coupling, respiration and protein import

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