Stability of antimicrobial decapeptide (KSL) and its analogues for delivery in the oral cavity.
OBJECTIVE
To investigate the stability of KSL, an antimicrobial decapeptide, and its analogues, in human saliva and simulated gastric fluid for delivery in the oral cavity.


METHODS
The degradation products of KSL in human saliva and simulated gastric fluid were separated by reversed-phase HPLC and their structures were identified by electrospray ionization-mass spectrometry. Analogues of KSL were synthesized by solid-phase synthesis procedure. Their enzymatic stabilities and antimicrobial activities were studied.


RESULTS
KSL was degraded by the peptide bond cleavages at Lys(6)-Val(7) in the human saliva and Phe(5)-Lys(6) in simulated gastric fluids. Three analogues of KSL were synthesized; the Lys(6) residue was either methylated (KSL-M), or replaced with Trp (KSL-W), or the d-form of Lys (KSL-D). The KSL analogues were much more stable than the native KSL, with the rank order of stability being KSL-D > KSL-W > KSL-M > KSL in human saliva. However, in simulated gastric fluid, while KSL-D was still stable, KSL-W was significantly degraded. In addition, KSL-D significantly lost the antimicrobial activity, whereas KSL-W completely preserved the activity against several oral bacteria. In a chewing gum formulation, KSL-W showed a more sustained release profile as compared with the native KSL.


CONCLUSIONS
This study suggests that KSL-W could be used as an antiplaque agent in a chewing gum formulation.
Na
Dong Hee
DH
College of Pharmacy, Kyungsung University, Busan, 608-736, South Korea.
Faraj
Jabar
J
Capan
Yilmaz
Y
Leung
Kai P
KP
DeLuca
Patrick P
PP
D000284:Administration, Oral; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002638:Chewing Gum; D002851:Chromatography, High Pressure Liquid; D003773:Dental Plaque / Q000517:prevention & control; D047630:Depsipeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004355:Drug Stability; D005750:Gastric Juice / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000737:chemistry; D013058:Mass Spectrometry; D008745:Methylation; D008826:Microbial Sensitivity Tests; D012463:Saliva / Q000737:chemistry*
D023181:Antimicrobial Cationic Peptides; D002638:Chewing Gum; D047630:Depsipeptides; C119235:lysyl-lysyl-valyl-valyl-phenylalanyl-lysyl-valyl-lysyl-phenylalanyl-lysine; C554541:lysyl-lysyl-valyl-valyl-phenylalanyl-tryptophyl-valyl-lysyl-phenylalanyl-lysine; D008239:Lysine