Journal of Peptide Science最新文献

Short neuropeptide F (sNPF) is an insect-specific neuropeptide named for its C-terminal phenylalanine. It consists of 6–19 amino acids with a conserved RLRFa structure, regulating feeding, growth, circadian rhythms, and water-salt balance in insects. Its receptor belongs to GPCR-As and binds sNPF to regulate the insect nervous system. Many research groups are evaluating sNPF for plant protection and pest control. In this study, the natural sNPF from the pea aphid (Acyrthosiphon pisum) was used as a lead compound. Five novel sNPF analogs were designed and synthesized through molecular docking and peptidomimetics, altering the N-terminal amino acid to Ser, Thr, Tyr, Leu, or Gln. Aphid bioassays showed that the analog I-3 (YLRLRFa, LC₅₀ = 1.820 mg/L) was more active than the natural Acypi-sNPF-1 and pymetrozine. The structure–activity relationship analysis indicated that N-terminal tyrosine incorporation, combined with increased ClogP and TPSA, enhanced aphidicidal activity. Furthermore, Toxtree's toxicity predictions suggest a low risk for all compounds, and a toxicity assay conducted on the honeybee (Apis mellifera) for I-3, which exhibits high aphidicidal activity, indicates that I-3 does not pose a toxicity risk to non-target organisms. Thus, I-3 can be utilized as a selective and environmentally friendly insecticide to manage pea aphids.

Peptides are molecules that consist of at least two amino acids linked by peptide bonds. The difference between peptides and proteins is primarily based on size and structure. Typically, oligopeptides consist of fewer than about 10–20 amino acids, and polypeptides consist of more than 20 amino acids, whereas proteins usually are made up more than 50 amino acids and often contain multiple peptide subunits as stated in the International Union of Pure and Applied Chemistry rules. Beyond the nutritional properties, peptides are also structural components of hormones, enzymes, toxins, and antibiotics and play several fundamental physiological roles in the body. Since the introduction of the first commercial peptide drug, insulin, peptide-based drugs have gained increased interest. So far, more than 80 peptide-based drugs have reached the market for a wide range of conditions, such as diabetes, cardiovascular diseases, and urological disorders. Meanwhile, peptides have also gained significant attention in the cosmetic industry because of their potential in boosting skin health. In this review, peptides were comprehensively summarized in the aspects of sources, function, the use of peptides in cosmetics and skin care, and indications for the delivery of cosmetic peptides.

Interactions between aromatic side chains of amino acids stabilize the fold and assembly of short peptides. The aromatic π…π and C-H…π interactions have been widely explored in the design of short peptides with specific folding and aggregation patterns. In the present study, we investigated the effect of homologated phenylalanine side chains on the conformation and assembly of peptide helices through X-ray crystallographic structure determination and analysis of five pentapeptides. The parent peptide Boc-Phe-Aib-Aib-Leu-Phe-NHiPr (1) and its four variations were synthesized, in which either one or both of the Phe side chains have been modified by inserting one (homophenylalanine, hPhe; -CH₂-CH₂-C₆H₅) or two (h²Phe; -CH₂-CH₂-CH₂-C₆H₅) additional CH₂ groups in the side chain, and their crystal structures were analyzed. The results show that intramolecular aromatic interactions are not present in the parent peptide but are present in the peptides containing the higher homologs of Phe. In peptides that did not show intramolecular aromatic interactions, the effect of increased length of the side chain of Phe residues manifested as intermolecular interactions leading to ordered packing in crystals. The results indicate the potential of hPhe and h²Phe residues to have aromatic interactions that could induce preferential folding and aggregation of peptides containing them.

Antimicrobial peptides (AMPs) are crucial constituents of inherent immunity and serve as vital components of human host defense, playing a pivotal role in combating invading microbial pathogens. Beyond their antimicrobial functions, AMPs also exhibit various other biological activities including apoptosis induction, wound healing promotion, and immune modulation. These peptides are found in various exposed tissues or surfaces throughout the body, such as eyes, skin, mouth, ears, respiratory tract, lungs, digestive, and urinary system. Additionally, certain AMPs such as LL-37, HNP, and lactoferrin have shown potential as candidates for anticancer activity. Given the limited selectivity between normal and cancer cells exhibited by many current immunotherapeutic agents, the inherent properties of AMPs make them promising candidates for cancer treatment. Their abundance, bioavailability, safety profile, efficiency, and harmony with the host immune system position them as attractive tools in the fight against cancer. This review is aimed at exploring the potential anticancer properties of AMPs and elucidating their relationship with immunology and cancer immunotherapy.

A de novo lanthanide-binding coiled-coil polypeptide (MB1–2) was previously reported to self-assemble into a trimeric complex upon addition of Tb³⁺ with a micromolar range dissociation constant. This study examines the effect of substitution of hydrophobic residues in heptad repeats of MB1–2 on the thermodynamic stability of the resulting Tb-peptide complex. Substitution of isoleucine to norleucine in each heptad repeat was assessed considering the greater accessible surface area of the latter and predicted increased hydrophobic interaction. Job's method of continuous variation using circular dichroism spectroscopy suggests a trimeric structure for the analog complex equivalent to that formed by MB1–2. The dissociation constant and CD spectra suggest that complex formation in the analog is more favorable as a result of ligand preorganization. In addition, thermal denaturation suggests greater stability of the Tb-MB1–2 Nle complex in comparison to the parent Tb-MB1–2. These results indicate improved stability of the complex class can be achieved through heptad repeat amino acid substitutions that increase peptide interchain interaction.

Guanylate cyclase C (GC-C), a receptor expressed on the apical membrane of intestinal mucosal cells, is activated by heat-stable enterotoxin (STa) produced by enterotoxigenic Escherichia coli, as well as the endogenous ligands guanylin and uroguanylin. In this study, novel peptides that interact with GC-C were generated using the cDNA display method, and their binding affinity and biological activity were evaluated. While the linear peptide library did not yield peptides with sufficient affinity for GC-C, three cyclic peptides (GCC-P1, GCC-P2, and GCC-P3), each containing two cysteine residues within a 15-residue sequence, were obtained from a cyclic peptide library containing nine-residue random sequences. GC-P2 exhibited significant binding affinity in Biacore assays, although the affinity was lower than those reported for known ligands. Notably, GCC-P2 and GCC-P3 demonstrated enhanced cGMP activity when used in combination with linaclotide. However, the agonist activity of these peptides was minimal, indicating that further modifications may be necessary to develop them for clinical applications. This study successfully extracted consensus sequences of peptide motifs that bind to GC-C from a highly diverse nine-residue random sequence library, which provides fundamental insights for the discovery and optimization of novel GC-C ligands.