Previously Os, a 22 amino acid sequence of a defensin from the soft tick Ornithodoros savignyi, was found to kill Gram‐positive and Gram‐negative bacteria at low micromolar concentrations. In this study, we evaluated synthetic peptide analogues of Os for antibacterial activity with an aim to identify minimalized active peptide sequences and in so doing obtain a better understanding of the structural requirements for activity. Out of eight partially overlapping sequences of 10 to 12 residues, only Os(3–12) and Os(11–22) exhibit activity when screened against Gram‐positive and Gram‐negative bacteria. Carboxyamidation of both peptides increased membrane‐mediated activity, although carboxyamidation of Os(11–22) negatively impacted on activity against Staphylococcus aureus. The amidated peptides, Os(3–12)NH2 and Os(11–22)NH2, have minimum bactericidal concentrations of 3.3 μM against Escherichia coli. Killing was reached within 10 minutes for Os(3–12)NH2 and only during the second hour for Os(11–22)NH2. In an E. coli membrane liposome system, both Os and Os(3–12)NH2 were identified as membrane disrupting while Os(11–22)NH2 was less active, indicating that in addition to membrane permeabilization, other targets may be involved in bacterial killing. In contrast to Os, the membrane disruptive effect of Os(3–12)NH2 did not diminish in the presence of salt. Neither Os nor its amidated derivatives caused human erythrocyte haemolysis. The contrasting killing kinetics and effects of amidation together with structural and liposome leakage data suggest that the 3–12 fragment relies on a membrane disruptive mechanism while the 11–22 fragment involves additional target mechanisms. The salt‐resistant potency of Os(3–12)NH2 identifies it as a promising candidate for further development. 相似文献
Type 2 diabetes mellitus (T2DM) is a multifactorial disease that requires multiple therapeutic strategies for its management. Bioactive peptides with multiple anti-diabetic targets are attractive therapeutic molecules. The present study was conducted to identify additional anti-diabetic targets of α-glucosidase inhibitory peptides, SVPA, SEPA, STYV, and STY. The α-glucosidase inhibitory activity of the peptides was in the order STYV?>?STY?>?SEPA?>?SVPA while molecular docking against human dipeptidyl peptidase IV (DPP-IV) showed that SVPA had the best binding affinity. In contrast, in vitro studies indicated that SEPA had a significantly higher (P?<?0.05) DPP-IV inhibitory activity (IC50?=?5.78?±?0.19 mM) than other peptides. SVPA and SEPA showed mixed inhibition pattern while STYV and STY were uncompetitive inhibitors of the enzyme. IPI (diprotin A), STYV and STY were not cytotoxic while SEPA displayed some cytotoxicity. In differentiated 3T3-L1 adipocytes, SVPA and STYV were found to induce a significant (P?<?0.05) decrease in intracytoplasmic lipid accumulation when added during the differentiation process while STY, GSH and IPI caused significant reduction (P?<?0.05) in the lipid accumulation when added after the differentiation. The SVPA, SEPA and STYV were better scavengers of methylglyoxal than STY but STYV had the best scavenging activities toward reactive oxygen species and nitric oxide. It was concluded that the four α-glucosidase inhibitory peptides including IPI have multiple targets against type T2DM but, overall, of the four peptides evaluated, STYV tends to have better potential for application as a multifunctional anti-diabetic peptide.
In humans, coping behaviour is an action taken to soothe oneself during or after a stressful or threatening situation. Some human behaviours with physiological functions also serve as coping behaviours, for example, comfort sucking in infants and comfort eating in adults. In birds, the behaviour of preening, which has important physiological functions, has been postulated to soothe individuals after stressful situations. We combine two existing modelling approaches - logistic regression and Darwinian dynamics - to explore theoretically how a behaviour with crucial physiological function might evolve into a coping behaviour. We apply the method to preening in colonial seabirds to investigate whether and how preening might be co-opted as a coping behaviour in the presence of predators. We conduct an in-depth study of the environmental correlates of preening in a large gull colony in Washington, USA, and we perform an independent field test for comfort preening by computing the change in frequency of preening in gulls that were alerted to a predator, but did not flee. 相似文献