The lung-stage schistosomulum has been regarded as the main target of protective immunity induced by radiation-attenuated vaccines (RAV) in the mouse model of schistosomiasis, and immune mechanisms mediated by the CD4+ Th1 response play a major role in the RAV model. To identify Th1 epitopes rapidly within molecules from the ...

Finding NEmo: In a mouse model for lung inflammation, the lipidated peptide-based ratiometric fluorescent reporter NEmo-2 indicates that neutrophil elastase (NE) activity is mainly associated with the surface of neutrophils, whereas a soluble reporter variant showed no activity in the lung fluid, likely because of the abundance of antiproteases. Targeting ...

TAT (a 13-mer derived from the HIV-1 Tat protein) linked cell-permeable peptides deliver plasma membrane impermeable cargos into the cell. We investigated the effect of a TAT linked intracellular third loop (IC3) of the endothelin-1 (ET-1) type B receptor on ET-1 activation of ERK. The effect of this peptide on ...

A novel cytotoxic cyclic pentadepsipeptide, neosansalvamide was produced by Fusarium solani KCCM90040 isolated from Fusarium contaminated potato in Korea. The molecular formula of neosansalvamide was analyzed as C32H50N4O6 by electrospray ionization mass/mass spectrometry and combined structural analysis. The one, two-dimensional nuclear magnetic resonance and absolute configuration of amino acids spectral ...

Using the membrane-modifying peptide, trichorovin-XIIa (TV-XIIa), which is an 11-residual peptaibol isolated from the fungus Trichoderma viride, we synthesized covalent conjugates of 20-mer oligonucleotide with TV-XIIa to examine the potential use of TV-XIIa in cellular delivery. The results indicated that the conjugates were progressively taken up by human lung carcinoma ...

Software advancements in the last several years have had a significant impact on proteomics from method development to data analysis. Herein, we detail a method, which uses our in-house developed software tool termed Skyline, for empirical refinement of candidate peptides from targeted proteins. The method consists of four main steps ...

The production of mycobactin (MBT) by Mycobacterium tuberculosis (Mtb) is essential for this bacterium to access iron when it is in an infected host. Due to this essential function, there is considerable interest in deciphering the mechanism of MBT assembly with the goal of targeting select biosynthetic steps for anti-tuberculosis ...

Anti-microbial peptides (AMPs) have therapeutic potential particularly for localized infections such as those of the lung. Here we show that airway administration of a pegylated AMP minimizes lung tissue toxicity while nevertheless maintaining anti-microbial activity. CaLL, a potent synthetic AMP (KWKLFKKIFKRIVQRIKDFLR) comprising fragments of LL-37 and cecropin A peptides, was ...

ABSTRACT: The authors would like to retract the article "Screening and Identification of a Renal Carcinoma Specific Peptide from a Phage Display Peptide Library". After the article was published it was revealed that the data in figure three, reported to show the Immunohistochemical staining of renal carcinoma, actually shows the ...

In this work, multifunctional biosynthetic hybrid nanostructures were prepared and studied for their potential utility in the recognition and inhibition of mRNA sequences for inducible nitric oxide synthase (iNOS), which are overexpressed at sites of inflammation, such as in cases of acute lung injury. Shell cross-linked knedel-like polymer nanoparticles (SCKs) ...

DevR is a key regulator of the dormancy response in Mycobacterium tuberculosis. Using DevR as bait to screen a phage display library, a peptide, DevRS1, was obtained. DevRS1 inhibited DevR-regulated transcription and survival of non-replicating tubercle bacilli in a hypoxia model of dormancy. DevRS1 peptide-mediated inhibition demonstrates the efficacy of ...

Mycobacterium avium complex (MAC) is a group of non-tuberculous mycobacteria that cause tuberculosis-like diseases in humans. Unlike Mycobacterium tuberculosis, MAC expresses high levels of glycopeptidolipids (GPLs) containing a well-defined tetrapeptide-amino alcohol core, composed of d-phenylalanine, d-allo-threonine, d-alanine, and l-alaninol, that is modified with a fatty acid and sugar residues. Surprisingly, ...

The extracellular matrix is a complex network of fibrous and nonfibrous molecules that not only provide structure to the lung but also interact with and regulate the behaviour of the cells which it surrounds. Recently it has been recognised that components of the extracellular matrix proteins are released, often through ...

θ-Defensins are cyclic octadecapeptides found in nonhuman primates whose broad antiviral spectrum includes HIV-1, HSV-1, severe acute respiratory syndrome coronavirus, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This study describes ...

Force-bearing tissues such as blood vessels, lungs, and ligaments depend on the properties of elasticity and flexibility. The 10 to 12 nm diameter fibrillin microfibrils play vital roles in maintaining the structural integrity of these highly dynamic tissues and in regulating extracellular growth factors. In humans, defective microfibril function results ...

BRICHOS domains are encoded in > 30 human genes, which are associated with cancer, neurodegeneration, and interstitial lung disease (ILD). The BRICHOS domain from lung surfactant protein C proprotein (proSP-C) is required for membrane insertion of SP-C and has anti-amyloid activity in vitro. Here, we report the 2.1 Å crystal structure of ...

We previously reported that a peptide-enriched soy sauce-like seasoning called fermented soybean seasoning (FSS) demonstrated antihypertensive effects both in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats. Angiotensin I-converting enzyme (ACE) inhibitory substances (9 kinds of dipeptides and a nicotianamine) were identified from FSS. In the present study, we clarified ...

Abstract Objectives. Proteomic technologies based on mass spectrometry are increasingly used as a valuable tool in clinical research allowing high-throughput protein and peptide profiling to be undertaken. Whilst previous research has focussed the application of this novel technology on the study of patients with disorders compared to comparable individuals from ...

Despite its long history of use and abuse in human culture, the molecular basis for alcohol action in the brain is poorly understood. The recent determination of the atomic-scale structure of GLIC, a prokaryotic member of the pentameric ligand-gated ion channel (pLGIC) family, provides a unique opportunity to characterize the ...

The toxic interaction of methanol, ethanol and propanol with bovine hemoglobin (BHb) at protein molecular level was studied by resonance light scattering (RLS), fluorescence, ultraviolet-visible absorption (UV-vis) and circular dichroism (CD) techniques. The experimental results showed that the three alcohols all had toxic effects on BHb and the effects increased ...

The endogenous cathelicidin peptide LL-37 is strongly expressed at the wound edge early in the process of acute wound healing, but only weakly expressed in chronic wounds. Excessive proteolysis may limit the therapeutic usefulness of exogenous LL-37, especially in ulcers colonized with Pseudomonas aeruginosa that produce elastase, which degrades LL-37. ...

We propose a new strategy of biomaterial design to achieve selective cellular degradation by the incorporation of cathepsin K-degradable peptide sequences into a scaffold structure so that scaffold biodegradation can be induced at the end of the bone formation process. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were used as a model ...

This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were ...

Therapeutic antibodies often suffer from degradation due to various modifications during storage. We detected a degradation of immunoglobulin gamma (IgG) 1 stored for 6 month at 40˚C, and identified the modification as the racemization of Cys 220 in the hinge sequence S²¹⁹CDKTHT²²⁵ of the heavy chain by tryptic peptide mapping ...

The O-specific polysaccharide (OPS) obtained by mild-acid degradation of the lipopolysaccharide isolated from Mesorhizobium huakuii strain S-52 was studied by sugar and ethylation analyses along with (1)H and (13)C NMR spectroscopy. It was concluded that the OPS was composed of trisaccharide repeating units containing two residues of 6-deoxy-l-talose (6dTal) and ...

The O-specific polysaccharide obtained by mild-acid degradation of lipopolysaccharide of Aeromonas bestiarum P1S was studied by sugar and methylation analyses along with (1)H and (13)C NMR spectroscopy. The sequence of the sugar residues was determined using (1)H,(1)H NOESY and (1)H,(13)C HMBC experiments. The O-specific polysaccharide was found to be a ...

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and mediates intracellular degradation of the LDLR. The amino-terminus of mature PCSK9, residues 31-53 of the prodomain, has an inhibitory effect on this function of PCSK9, but the underlying mechanism is not ...

The hypothalamus is the central regulatory region of the brain that links the nervous system to the endocrine system via the pituitary gland. It synthesizes and secretes neuropeptide hormones, which in turn act to stimulate or inhibit the secretion of pituitary hormones. We have undertaken a detailed MS investigation of ...

Citric acid is widely used to buffer pharmaceutical formulations including protein pharmaceuticals. In accelerated stability studies of the small cyclic peptide oxytocin, we have noted that additional degradation products form when oxytocin is formulated in citrate that do not form in other common buffers such as acetate and phosphate. Using ...

Human neuropeptide Y (NPY) is an important biologics that regulates multitude of physiological functions and could be amenable to therapeutic manipulations in certain disease states. However, rapid (minutes) enzymatic degradation and inactivation of NPY precludes its development as a drug. Accordingly, we determined whether self-association of NPY with biocompatible and ...

Opportunistic human pathogens of the genus Providencia from the family Enterobacteriaceae are serotyped by their O-antigens, which represent the O-polysaccharide chains of the lipopolysaccharides (LPSs) on the cell surface. In this work, the O-polysaccharide of Providencia alcalifaciens O9 was obtained by mild acid degradation of a long-chain S-form LPS. The ...

Nowadays, the analysis of the uptake and intracellular distribution of cell-penetrating peptides mostly relies on fluorescence microscopy, using fluorescently labeled CPP analogs. However, fluorescence microscopy does not reveal to which degree fluorescence reflects the intact peptide or only breakdown products. Here, we introduce fluorescence correlation spectroscopy (FCS) as a powerful ...

Peptide biomarkers in plasma or serum are subject to proteolytic degradation caused by intrinsic peptidase activities, resulting in a potential barrier in translating a discovered biomarker into clinical application. This chapter describes a method using time-course MALDI-TOF MS analysis to investigate the stability of a plasma peptide biomarker under a ...

We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called "SEVI" and enhance HIV-1 infection in vitro. In order to understand the ...

We demonstrate a supramolecular peptide separation approach by the selective immobilization of peptides bearing an N-terminal tryptophan onto a CB[8]-modified gold substrate, followed by electrochemical release. The CB[8]-stabilized heteroternary complexes were characterized by (1)H NMR, ESI-MS, UV/vis, and fluorescence spectroscopy and cyclic voltammetry. Micropatterned CB[8]-modified gold substrates were found to ...

Insulin-degrading enzyme (IDE) can degrade insulin and amyloid-β, peptides involved in diabetes and Alzheimer's disease, respectively. IDE selects its substrates based on size, charge, and flexibility. From these criteria, we predict that IDE can cleave and inactivate ubiquitin (Ub). Here, we show that IDE cleaves Ub in a biphasic manner, ...

[Cu(II)(M(a))(M(b))](•2+) complexes, where M(a) and M(b) are dipeptides or tripeptides each containing either a tryptophan (W) or tyrosine (Y) residue, have been examined by means of electrospray tandem mass spectrometry. Collision-induced dissociations (CIDs) of complexes containing identical peptides having a tryptophan residue generated abundant radical cations of the peptides; by ...

Cooperative behavior is widely spread in microbial populations. An example is the expression of an extracellular protease by the lactic acid bacterium Lactococcus lactis, which degrades milk proteins into free utilizable peptides that are essential to allow growth to high cell densities in milk. Cheating, protease-negative strains can invade the ...

Peptide dendrimers are attractive nonviral gene vectors. But a biological barrier for their application in gene delivery is the fast degradation catalyzed by proteasomes. Proteasome inhibitors are efficient at prohibiting the degradation of peptide nonviral vectors, thus enhancing gene transfection efficiency. In this study, N(α)-Boc-protected leucine vinyl ester proteasome inhibitor ...

We used picosecond transient absorption and fluorescence lifetime spectroscopy to study singlet exciton annihilation and depolarization in self-assembled aggregates of meso-tetra(4-sulfonatophenyl)porphine (TPPS(4)) and a synthetic 22-residue polypeptide. The polypeptide was designed and previously shown to bind three TPPS(4) monomers via electrostatic interactions between the sulfonate groups and cationic lysine residues. ...

The N-terminal domain of human topoisomerase IB has been expressed, purified and characterized by spectroscopic techniques. CD spectra as a function of concentration and pH indicate that the domain does not possess any defined secondary structure. The protein is probably in a natively unfolded state since its denaturation curve is ...

Intraneuronal accumulation of ubiquitin conjugates is a pathological feature of neurodegenerative disorders such as Alzheimer's disease (AD). Previous reports propose that accumulation of ubiquitinated species in AD is a result of inhibition of proteasomal activity by amyloid-β (Aβ) peptides, which leads to blocking of ubiquitin-dependent protein degradation by the proteasome. ...

In the search for methods to study structure and function of membrane-associated proteins and peptides flow linear dichroism, LD, spectroscopy has emerged as a promising technique. Using shear-aligned lipid vesicles, conformations and binding geometries of membrane-bound bio-macromolecules can be assessed. Here we investigate anchoring properties and specific orientations of tryptophan ...

Tyrosine side chains are involved in proton coupled electron transfer reactions (PCET) in many complex proteins, including photosystem II (PSII) and ribonucleotide reductase. For example, PSII contains two redox-active tyrosines, TyrD (Y160D2) and TyrZ (Y161D1), which have different protein environments, midpoint potentials, and roles in catalysis. TyrD has a midpoint ...

A disruptive interaction of phosphoserine with tryptophan in peptides that autonomously fold into a β-hairpin structure in aqueous solution was explored in a positional context within the hairpin structure. All the peptides presented here have a serine or phosphoserine directly cross strand from a tryptophan residue in the β-hairpin structure. ...

This communication reports morphological studies of a novel C(3)-symmetric thiolated, tren-based ditryptophan conjugate. The exposed thiol groups on the soft structures interacted with gold nanoparticles and mediated the release of encapsulated fluorescent dye, when exposed to natural sunlight.

A novel long lifetime fluorescence reporter based on 9-aminoacridine was designed, the lifetime of which can be modulated in a defined manner when in proximity to a tryptophan residue enabling fluorescence lifetime based biochemical assays to be configured.

EGF receptor-binding peptides could be found by a peptide screening method using fifteen fluorescent amino acids as fluorescent tags. Of 225 peptides, we found an 8-mer peptide containing a dipeptide unit, Y-F, which was the strongest binding peptide to the EGF receptor.

We report the first structure determination of a covalent photoadduct between a Ru(II)-tap complex and a tryptophan-containing peptide (AlaTrpAla) by mass spectrometry and NMR spectroscopy. Ru(II)-tap complexes could thus be exploited as photodamaging agents of Trp-containing polypeptides or proteins.

p-Cyanophenylalanine is an extremely useful fluorescence probe of protein structure that can be recombinantly and chemically incorporated into proteins. The probe has been used to study protein folding, protein-membrane interactions, protein-peptide interactions, and amyloid formation; however, the factors that control its fluorescence are not fully understood. Hydrogen bonding to the ...