內因性 Opioid Peptides와 精神病

李正浩 인제대학교 1981 仁濟醫學 Vol.2 No.4

최근 동물과 인간의 뇌에서 Opiate 수용체들이 발견이 되고 체내에서 생산된 내인성 Opioid Peptides의 발견으로 이들 Peptides와 정신병 특히 정신분열증과 어떤 관계가 있지않나 하고 이 방면에 대한 연구가 활발하게 진행되고 있다. 이에 본 저자는 내인성 Opioid Peptides와 정신병 특히 정신분열증과의 관계에 대한 지금까지의 연구결과들을 전반적으로 정리하여 알아보고져 한다. Recent discovery of opiate receptors in animal and human brains and identification of endogenously produced opioid peptides have led to many studies about effects and relatedness of endogenous opioid peptides in psychoses, especially schizophrenia. In spite of enthusiastical studies about this field, the results are yet contradictory. The results of the studies can be grouped into two categories: One category is that in which no relation could be identified between the peptides and psychoses. The other category that showed some correlation could furhter be divided into two groups. The first one is that the schizophrenic symptoms may be related with increased level or overactivity of endogenous opioid peptides in human central nervous system, and the other one is that the schizophrenic symptoms may be related with lowered level or deficient activity of endogenous opioid peptides in human central nervous system. The author attempted to overview the anatomical distribution, pharmacological actions of endogenous opioid peptides, and the results of recent studies showing some relatedness between endogenous opioid peptides and psychoses, especially schizophrenia.

고정화 효소를 이용한 명태고기풀 수세액으로부터 Peptide 생산에 관한 연구

신석우,말강방남,SHIN Suk-U,SUETSUNA Kunio 한국수산과학회 1997 한국수산과학회지 Vol.30 No.3

명태 (Alask pollack, Theragia chalcogramma) 고기풀 수세액 중의 단백질 활용방안으로 기능성 peptide생산을 위해 고정화 protease를 이용한 생물반응기에서 가수분해하여 gel 여과후 정제 peptide의 특성 및 아미노산 존재 여부를 파악하기 위해 실험한 결과는 다음과 같다. 1. $0.5\%$ 농도의 고기를 수세액을 반응온도 $50^{\circ}C$에서 24시간 가수분해 하였을 때 분해율은 $50\%$ (OPA법)였다. 2. Sephadex G-50 column chromatography에 의한 고기풀 수세 액과 조peptide의 분자량은 각각 $10,000\~50,000Da$과, $600\~12,000Da$의 광범위한 분포를 나타내었다. 3. SP-Sephadex C-25 $(H^+)$ column chromatography에서 식염농도 $0\~3\%$의 농도구배에서 $0.6\~0.9\%\;NaCl$, pH 2 범위에서 염기성이 약한 아미노산을 함유하였고, $1.2\~2.0\%$에서는 염기성이 강한 아미노산을 함유하는 peptide가 용출되었다. 4. SP-Sephadex C-25 ($(H^+)$ column chromatography에서 분획한 SP-분획을 Sephadex G-50 colum chromatography에서 peptide의 분자량 측정 결과는 대게 저분자로 분자량 1,000Da에서 3,000Da 범위였고, SP-4>SP-3>SP-2>SP-1의 순으로 분자량 분포를 나타내었다. 5. 정제 peptide의 아미노산 조성은 수세 peptide에서 glycine, arginine이 가장 많이 함유하였으며 그외 glutamic acid, alanine, aspartic aicd 등이였고, SP-분획 peptide는 수세 peptide와 대동소이하였으나 SP-2에서 glycine이 $33\%$로 가장 높았다. Peptides separated from fish paste washing liquid of an Alaska pollak (Theragria chalcogramma) were purified and characterized. The fish paste washing liquid (supernatant) was separated by centrifugation of fish paste homogenate. The fish paste washing liquid of $0.5\%$ concentration was hydrolyzed for 24 hour at $50^{\circ}C$ by immobilized protease in bioreactor and decomposing liquid of protein having $50\%$ decomposing rate (OPA method) was obtained. The crude peptide fractions were obtained from this liquid by Dowex 50w $(H^+)$ column chromatograpy. Purified peptides (SP-fraction peptides) were fractionated by using SP-Sepadex C-25 $(H^+)$ column chromatography. Molecular weights and amino acid compositions of these peptides were estimated by Sephadex G-50 column chromatography and HPLC, respectively. when the washed peptides was eluated with $0.6\~0.9\%\;and\;1.2\~2.0\%$ of NaCl, peptides composed of weakly basic amino acids and strongly basic amino acid were respectively eluted. Molecular weights of each peptide fractions showed the broad distribution from 1,000 Da to 3,000 Da in the order of SP-4>SP-3>SP-2>SP-1. Peptides contained a large quantity of glycine, arginine, glutamic acid, and alanine in the washed peptide and its SP-tractions, respectively.

카제인 유래 생리활성 Peptide의 체내 효과

정호정,민복기,곽해수,Jung, Ho-Jung,Min, Bock-Ki,Kwak, Hae-Soo 한국축산식품학회 2009 한국축산식품학회지 Vol.29 No.6

Casein is considered to be the main source of protein in milk; therefore, many studies have been conducted to identify casein-derived bioactive peptides and their physiological effects. Casein is inactive within the parent protein but can be liberated by various proteases and enzymatic hydrolysis during microbial fermentation and gastrointestinal digestion. Once absorbed, casein exhibits different bioavailabilities in the body. Specifically, casein-derived peptides function as angiotensin converting enzyme (ACE) inhibitor in the cardiovascular system; thus, they are expected to reduce and prevent hypertension. Additionally, casein-derived peptides behave as opioid-like peptides in the nervous system, which impacts relaxation. These peptides are also expected to modulate various aspects of immune functions. Finally, caseinophosphopeptide (CPP) and glycomacropeptide (GMP) may exhibit a number of nutritional effects such as the absorption of calcium, iron or zinc. Many studies have been conducted to evaluate casein-derived peptides due to their multifunctional properties and the results of these studies have contributed to the development of a wide variety of functional dairy products. The purpose of this paper was to review the generation of bioactive peptides, their absorption and metabolism, and their specific bioactive effects.

Bioactive Peptides and Its Alternative Processes: A Review

Norfahana Abd-Talib,Emmy Liza Anak Yaji,Nur Suraya Abd Wahab,Nadia Razali,Kelly Yong Tau Len,Jumardi Roslan,Nazamid Saari,Khairul Faizal Pa’ee 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.3

Bioactive peptides are molecules of paramount importance with significant health benefits. These bioactive peptides extracted from various food sources demonstrated significant bioactivity and potency, including angiotensinconverting enzyme inhibitors, antioxidants, opioids, and antimicrobials. However, various challenges hindered the industrial-scale production of peptides, such as the sensory performance of peptides due to bitterness, low peptides bioavailability and yield, minimal human tests, unconfirmed molecular mechanisms, and the sustainability of the resources for mass production. The emerging alternative processes such as high hydrostatic pressure, microwave, ultrasound, sub- and supercritical fluids are selectively beneficial, albeit time-consuming and expensive. The diversity of the properties of bioactive peptides complicates the design of the appropriate purification steps, particularly for novel peptides. The integrative process by coupling the production and purification of bioactive peptides to a single integrative system can be a way forward for bioactive peptides production with high purity, potency, and cost-effectiveness. Thus, the review provides a comprehensive insight into the current status, trends, and challenges of bioactive peptide production through conventional and emerging processes. Meanwhile, the potential technological leap through integrative processes is also featured as the sustainability of the process must be assured.

Development of functional materials using insect antibiotic peptides

Jae Sam Hwang,Joon Ha Lee,In-Woo Kim,Minchul Seo,Mi-Ae Kim 한국응용곤충학회 2018 한국응용곤충학회 학술대회논문집 Vol.2018 No.10

Insect antimicrobial peptides (AMPs) have been characterized more than 150 peptides since identification of cecropin in the hemolymph of pupae from Hyalophora cecropia in 1980. Therefore, it is considered that insects are good species of AMPs selection. Insect AMPs are small (below 10 kDa), cationic, and amphipathic with variable length, sequence, and structure. They perform a critical role on humoral immunity in the insect innate immune system against invading pathogens such as bacteria, fungi, parasites, and viruses. Most of insect AMPs are induced rapidly in the fat bodies and other specific tissues of insects after septic injury or immune challenge. Then the AMPs subsequently released into the hemolymph to act against microorganisms. These peptides have a broad antimicrobial spectrum against various microorganisms including anticancer activities. Insect AMPs can be divided into four families based on their structures and sequences. That is α-helical peptides, cysteine-rich peptides, proline-rich peptides, and glycine-rich peptides/proteins. For instance, cecropins, insect defensins, proline-rich peptides, and attacins are common insect AMPs, but gloverins and moricins have been identified only in lepidopteran species. In this presentation, we focus on AMPs from insects and discuss current knowledge and recent progresses with potential application of insect AMPs.

Identification of Antimicrobial Peptide Hexamers against Oral Pathogens through Rapid Screening of a Synthetic Combinatorial Peptide Library

Je-seon Song,Kyung Joo Cho,Joungmok Kim,Jeong Hee Kim KOREAN ACADAMY OF ORAL BIOLOGY 2014 International Journal of Oral Biology Vol.39 No.4

A positional scanning synthetic peptide combinatorial library (PS-SCL) was screened in order to identify antimicrobial peptides against the cariogenic oral bacteria, Streptococcus mutans. Activity against Streptococcus gordonii and Aggregatibacter actinomycetemcomitans was also examined. The library was comprised of six sub-libraries with the format O(1-6)XXXXX-NH2, where O represents one of 19 amino acids (excluding cysteine) and X represents equimolar mixture of these. Each sub-library was tested for antimicrobial activity against S. mutans and evaluated for antimicrobial activity against S. gordonii and A. actinomycetemcomitans. The effect of peptides was observed using transmission electron microscopy (TEM). Two semi-mixture peptides, RXXXXN-NH2 (pep-1) and WXXXXN-NH2 (pep-2), and one positioned peptide, RRRWRN-NH2 (pep-3), were identified. Pep-1 and pep-2 showed significant antimicrobial activity against Gram positive bacteria (S. mutans and S. gordonii), but not against Gram negative bacteria (A. actinomycetemcomitans). However, pep-3 showed very low antimicrobial activity against all three bacteria. Pep-3 did not form an amphiphilic α -helix, which is a required structure for most antimicrobial peptides. Pep-1 and pep-2 were able to disrupt the membrane of S. mutans. Small libraries of biochemically-constrained peptides can be used to generate antimicrobial peptides against S. mutans and other oral microbes. Peptides derived from such libraries may be candidate antimicrobial agents for the treatment of oral microorganisms.

Antibacterial Activities of Peptides Designed as Hybrids of Antimicrobial Peptides

Shin, Song-Yub,Kang, Joo-Hyun,Lee, Myung-Kyu,Hahm, Kyung-Soo Korean Society for Biochemistry and Molecular Biol 1996 Journal of biochemistry and molecular biology Vol.29 No.6

CA(1-8)ME(1-12), the CA-ME hybrid peptide of the amino terminal segments of cecropin A (CA) and melittin (ME), has been reported to have a broad spectrum and improved potency without a hemolytic property. In order to obtain new synthetic peptides with powerful antibacterial activity without hemolytic activity, several hybrid peptides were designed from the sequences of CA, ME, magainin 2, bombinin and lactoferricin. All hybrid peptides were constructed to form an amphipathically basic-flexible-hydrophobic structure and synthesized by the solid phase method. Their hemolytic activities against human red blood cells and antibacterial activities against both Gram-positive and Gram-negative bacteria were detennined. CA(1-8)MA(1-12), CA(1-8)BO(1-12), MA(10-17)ME(1-12) and LF(20-29)ME(1-12) showed comparable activities with broad spectra against both Gram-positive and Gram-negative bacteria relative to CA(1-8)ME(1-12) but without hemolytic properties. These hybrid peptides, therefore, could be useful as model peptides to design a novel peptide with improved antibacterial activity and study on structure-activity relationships of antimicrobial peptides.

Applications of Circular Dichroism for Structural Analysis of Gelatin and Antimicrobial Peptides

Gopal, Ramamourthy,Park, Jin Soon,Seo, Chang Ho,Park, Yoonkyung Molecular Diversity Preservation International (MD 2012 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.13 No.3

<P>Circular dichroism (CD) is a useful technique for monitoring changes in the conformation of antimicrobial peptides or gelatin. In this study, interactions between cationic peptides and gelatin were observed without affecting the triple helical content of the gelatin, which was more strongly affected by anionic surfactant. The peptides did not adopt a secondary structure in the presence of aqueous solution or Tween 80, but a peptide secondary structure formed upon the addition of sodium dodecyl sulfate (SDS). The peptides bound to the phosphate group of lipopolysaccharide (LPS) and displayed an alpha-helical conformation while (KW)<SUB>4</SUB> adopted a folded conformation. Further, the peptides did not specifically interact with the fungal cell wall components of mannan or laminarin. Tryptophan blue shift assay indicated that these peptides interacted with SDS, LPS, and gelatin but not with Tween 80, mannan, or laminarin. The peptides also displayed antibacterial activity against <I>P. aeruginosa</I> without cytotoxicity against HaCaT cells at MIC, except for HPA3NT3-analog peptide. In this study, we used a CD spectroscopic method to demonstrate the feasibility of peptide characterization in numerous environments. The CD method can thus be used as a screening method of gelatin-peptide interactions for use in wound healing applications.</P>

Prophylactic and Therapeutic Potential of Asp f1 Epitopes in Naïve and Sensitized BALB/c Mice

Neelkamal Chaudhary,Lakshna Mahajan,Taruna Madan,Anil Kumar,Gajendra Pratap Singh Raghava,Seturam Bandacharya Katti,Wahajul Haq,Puranam Usha Sarma 대한면역학회 2009 Immune Network Vol.9 No.5

Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naïve mice and challenged with Afu-allergens/ antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results: Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5∼ 98.9%) and IgG antibodies (45.7∼71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4∼88%) and IgG antibodies (15∼54%). Increased IgG2a/IgG1 and IFN-γ/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells’ infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans. Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naïve mice and challenged with Afu-allergens/ antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results: Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5∼ 98.9%) and IgG antibodies (45.7∼71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4∼88%) and IgG antibodies (15∼54%). Increased IgG2a/IgG1 and IFN-γ/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells’ infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans.

Peptides as drug delivery vehicles across biological barriers

Debadyuti Ghosh,Xiujuan Peng,Jasmim Leal,Rashmi P. Mohanty 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.1

Peptides are small biological molecules that are attractive in drug delivery and materials engineering for applications including therapeutics, molecular building blocks and cell-targeting ligands. Peptides are small but can possess complexity and functionality as larger proteins. Due to their intrinsic properties, peptides are able to overcome the physiological and transport barriers presented by diseases. In this review, we discuss the progress of identifying and using peptides to shuttle across biological barriers and facilitate transport of drugs and drug delivery systems for improved therapy. Here, the focus of this review is on rationally designed, phage display peptides, and even endogenous peptides as carriers to penetrate biological barriers, specifically the blood–brain barrier (BBB), the gastrointestinal tract (GI), and the solid tumor microenvironment (T). We will discuss recent advances of peptides as drug carriers in these biological environments. From these findings, challenges and potential opportunities to iterate and improve peptide-based approaches will be discussed to translate their promise towards the clinic to deliver drugs for therapeutic efficacy.