Novel anti-inflammatory peptides as cosmeceutical peptides

Ultraviolet (UV) radiation induced inflammation plays an important role in the aging of human skin. Prostaglandin (PG) E₂ is the primary mediator of UVB induced photoinflammation. We screened an internal library for dipeptides that inhibited UVB induced PGE₂ synthesis but showed no cytotoxicity toward human keratinocytes. We identified three highly active inhibitory sequences, LE (Leu + Glu), MW (Met + Trp) and MY (Met + Tyr). To evaluate their efficacy in human skin, 24 sites of abdomen skin were irradiated with a 308 nm excimer laser (300 mJ/cm²), after which 2% LE, MW, MY or a control were applied to the irradiated sites for 24 h. The erythema index (EI) was measured before and 24 h after treatment. The results showed that LE and MW significantly decreased UVB induced erythema (p = 0.041 and p = 0.036, respectively), but ME did not. Overall, LE and MW are candidate cosmeceutical peptides that can protect skin from UVB induced photoinflammation.     

Antibacterial activities of peptides designed as hybrids of antimicrobial peptides

Hybrid peptides (HP-MA, HP-ME), each of 20 residues and incorporating 2–9 residues of Helicobacter pylori ribosomal protein L1 (HP) and 1–12 residues of magainin 2 and melittin, were designed. The antibiotic activities of these peptides were evaluated using bacterial, tumor and human erythrocyte cells. HP-MA had a stronger antibacterial activity against Gram-positive bacteria and Gram-negative bacteria than HP (2-20) and magainin 2, and HP-ME was similar to melittin. None of the hybrids had anti-tumor or hemolytic activity. These peptides were further investigated using an artificial liposomal vesicle and 1,6-diphenyl-1,3,5-hexatriene as a membrane probe, and confirmed to have similar antibacterial activities. The antibacterial effect of these hybrids is probably caused by their ability to damage the bacterial plasma membrane. Additional circular dichroism spectra suggested that the -helical structure of these peptides plays an important role in their antibiotic effect but that -helical property is less connected with the enhanced antibiotic activity.     

Oostatic peptides

Oostatic peptides are organic molecules, which influence an insect reproduction due to a regulation of the eggs development. It was proved that decapeptide—H-Tyr-Asp-Pro-Ala-Pro-Pro-Pro-Pro-Pro-Pro-OH (YDPAPPPPPP)—isolated from mosquito Aedes aegypti, inhibits trypsin activity in the midgut of the mosquito. Therefore, it was named trypsin-modulating oostatic factor (Aea-TMOF). Feeding the recombinant cells with cloned and expressed TMOF on the coat protein of tobacco mosaic virus (TMV) to mosquito larvae, caused larval mortality. The TMOF was therefore designed for usage as a new biorational insecticide against mosquito. Similarly, a hexapeptide—H-Asn-Pro-Thr-Asn-Leu-His-OH (NPTNLH)—was isolated from the grey flesh fly Neobellieria bullata. This peptide and some of its analogs inhibited trypsin-like synthesis by the midgut in female flies and was therefore entitled Neb-TMOF. Interestingly, the synthetic Aea-TMOF and mainly its C-terminus shorten analogs, including those containing D-amino acids or methylene-oxy isosteric bond, quickly and strongly inhibited the hatchability and egg development in the flesh fly N. bullata.     

Therapeutic peptides

Novel peptide therapeutics are increasingly making their way into clinical application. Indeed, certain naturally derived peptides have been successful drugs for many years. With the advent of large biological and synthetic peptide libraries and high-throughput screening, many promising candidates could soon be added to the list of peptides under development. These advances have introduced new strategies for the administration of peptide drugs and improvements of clearance half-lives in vivo. Despite the potential obstacles that remain, peptide therapeutics are poised to play a significant role in the treatment of diseases ranging from Alzheimer's disease to cancer.     

Prolactin-releasing peptides

Physiologic control of prolactin (PRL) secretion is largely dependent upon levels of dopamine accessing the adenohypophysis via the hypophysial portal vessels. However, it is clear that other factors of hypothalamic origin can modulate hormone secretion in the absence or presence of dopamine. Several neuropeptides have been identified as PRL releasing factors (PRFs) but none of these peptides appears to be a major determinant of PRL secretion in vivo. There remain uncharacterized activities in hypothalamic extracts that can alter secretion and production of the hormone. In addition, there exist a wide variety of substances (neurotransmitters, neuromodulators, neuropeptides) that can act within the hypothalamus to modify the neuroendocrine regulation of PRL secretion. These factors may not be considered true PRFs because their actions are not exerted directly at the level of the lactotroph; however, they can act in brain to stimulate PRL release in vivo and therefore might be considered PRL releasing peptides (PRPs).     

Opioid peptides

This review was presented as an overview at the meeting of the American Society for Pharmacology and Experimental Therapeutics in Portland, Oregon, in August, 1979. The intent of the talk was to briefly survey the current status of the field and to present some ideas as to future research. No attempt was made at an exhaustive review of the literature.     

CART peptides

CART peptides are among the newest putative peptide neurotransmitter/cotransmitters. They show no significant homology to any other peptide, and they are thought to have a role in reward and reinforcement, feeding, development, sensory processing, stress and endocrine control.     

TRH-like peptides

TRH-like peptides are characterized by substitution of basic amino acid histidine (related to authentic TRH) with neutral or acidic amino acid, like glutamic acid, phenylalanine, glutamine, tyrosine, leucin, valin, aspartic acid and asparagine. The presence of extrahypothalamic TRH-like peptides was reported in peripheral tissues including gastrointestinal tract, placenta, neural tissues, male reproductive system and certain endocrine tissues. Work deals with the biological function of TRH-like peptides in different parts of organisms where various mechanisms may serve for realisation of biological function of TRH-like peptides as negative feedback to the pituitary exerted by the TRH-like peptides, the role of pEEPam such as fertilization-promoting peptide, the mechanism influencing the proliferative ability of prostatic tissues, the neuroprotective and antidepressant function of TRH-like peptides in brain and the regulation of thyroid status by TRH-like peptides.     

Therapeutic peptides: technological advances driving peptides into development

As potential therapeutics, peptides offer several advantages over small molecules (increased specificity) and antibodies (small size). Nevertheless, a number of key issues have hampered their use as drug candidates. A series of new technologies have recently been developed that allow peptides to be viable drug candidates in areas usually restricted to protein therapeutics, such as monoclonal antibodies. These include the development of various types of peptide-conjugates that have lower rates of clearance and hence the potential to increase the exposure of peptide drug candidates in chronic diseases. Structural additions have also been made to peptides, including the use of unnatural amino acids, mainchain modifications and other novel substitutions, which have helped to improve peptide stability and further their therapeutic potential.     

抗菌肽活性及天然抗菌肽的改造

抗菌肽具有抗菌谱广、热稳定性强、分子量小及免疫原性小等特点,其杀菌机制独特,病原菌不易产生耐药性,有望开发成新一代肽类抗生素。本文主要综述了影响抗菌肽生物活性的生化性质,即螺旋度、疏水性、两亲性、正电荷数等,并从结构的角度论述了其对抗菌肽抑菌活性的影响。部分抗菌肽具有空间结构不稳定、溶血活性等缺点,限制了其临床应用。因此,对天然抗菌肽的改造也成为目前抗菌肽的研究热点,本文还综述了天然抗菌肽的改造方法。     

Immunopharmacology of muramyl peptides

In recent years the immunomodulatory activity of muramyl peptides has become of major interest because of their possible physiological and clinical importance. Many data suggest that this group of compounds has other pharmacological activities besides effects on the immune system. Some of these effects, such as pyrogenicity, sleep enhancement, and analgesic activity, are linked to the central nervous system (CNS). Other activities of muramyl peptides may involve CNS and peripheral mechanisms. These include antiinflammatory and hepatoprotective activities and the effect of muramyl peptides on blood pressure. The multiplicity of pharmacological actions of muramyl peptides suggests that these compounds might have a general modulatory role in physiological functions.     

Large-scale synthesis of peptides

Recent advances in the areas of formulation and delivery have rekindled the interest of the pharmaceutical community in peptides as drug candidates, which, in turn, has provided a challenge to the peptide industry to develop efficient methods for the manufacture of relatively complex peptides on scales of up to metric tons per year. This article focuses on chemical synthesis approaches for peptides, and presents an overview of the methods available and in use currently, together with a discussion of scale-up strategies. Examples of the different methods are discussed, together with solutions to some specific problems encountered during scale-up development. Finally, an overview is presented of issues common to all manufacturing methods, i.e., methods used for the large-scale purification and isolation of final bulk products and regulatory considerations to be addressed during scale-up of processes to commercial levels.