Amino Acid Derivatives

This pTHrP fragment stimulated membrane-associated protein kinase C in freshly isolated rat spleen lymphocytes and thus raises the possibility of being a physiological regulator of the proliferation and other activities of lymphocytes.

Apelin-17 is an endogenous ligand of the human orphan G protein-coupled receptor APJ, reported to act as a coreceptor of CD4 for human and simian immunodeficiency viruses. Apelin-17 and apelin-13 represent the predominant molecular forms of apelin present in the whole brain, hypothalamus, and plasma. Like apelin-13, apelin-17 exhibited a high activity on extracellular acidification rate and strongly inhibited forskolin-stimulated cAMP production in CHO cells expressing the human or the rat apelin receptor. The peptide might play a crucial role in the maintenance of body fluid homeostasis by counteracting AVP (arginine vasopressin) actions through inhibition of AVP neuron activity and AVP release.

Non-mammalian Arg-vasopressin/oxytocin analog.

Suc-AAA-pNA, a readily soluble and sensitive substrate for human and rat neutrophil and porcine pancreatic elastases. The trialanine substrate is also hydrolyzed by proteinase K, subtilisins and thermitase as well as by astacin, a crayfish zinc-endopeptidase.

<p>Bachem ID: 4007171.</p>

A good substrate for carboxypeptidases B and N.

Competitive inhibitor of alanine racemase, Ki 0.005 mM.

<p>Bachem ID: 4004112.</p>

Vasotocin (AVT, argiprestocin) is the vasopressin/oxytocin analog produced in birds, amphibians and fish. AVT shows antidiuretic as well as reproductive activities.

In vitro, this compound competitively inhibited sweetalmond β-glucosidase (Ki = 17 µM).

The peptidylprolyl isomerase substrate Suc-AAPF-AMC is also hydrolyzed by carboxypeptidase Y, cathepsin G, and chymotrypsin. Suc-AAPF-AMC has also been used to analyze the chymotrypsin-like activity of trypsins.

Rat pTH (1-34) suppressed appositional bone formation by cultured rat cranial osteoblasts.

Thymopentin (TP5), an active fragment of thymopoietin (TP), reduces endocrine and behavioral responses to experimental stress, possibly by lowering plasma TP (pTP) levels. The immunomodulatory peptide suppresses proliferation and induces differentiation in HL-60 cells.

Z-VAD(OMe)-FMK, a pan-caspase inhibitor, is a competitive irreversible peptide inhibitor and blocks caspase-1 family and caspase-3 family enzymes. The methyl ester of Z-VAD-FMK has been used in studies to support the hypothesis that inhibitors of caspases can limit brain infarction resulting from the permanent obstruction of a brain artery.

Endogenous kappa-opioid receptor agonist. It is suggested that it attenuates galanin-induced impairment of memory processes through the mediation of kappa-opioid receptors.

<p>Bachem ID: 4030577.</p>

<p>Bachem ID: 4001907.</p>

Sensitive fluorogenic substrate for trypsin, soybean trypsin-like enzyme, and papain.

Substrate for assays of aminopeptidase M and leucine aminopeptidase. Its use for histochemical purposes has been described.

Arginine oligomers as heptaarginine, either alone or when conjugated to therapeutic agents or large biopolymers, have been shown to cross readily a variety of biological membranes (e.g. lipid bilayers and epithelial tissue). The importance of the guanidinium group in transport was supported by the observation that short oligomers of arginine entered cells far more rapidly than the corresponding oligomers of either lysine, histidine, ornithine, or citrulline.

Suc-AAA-AMC, sensitive fluorogenic substrate for pancreatic elastase.

Glucagon sulfoxide shows the same maximal glucose mobilizing activity in rat hepatocytes as native glucagon, but it is less potent, suggesting a crucial role of methionine in the binding of glucagon to its hepatic receptor.

α-Melanotropin, also known as α-melanocyte-stimulating hormone (α-MSH), is a 13-amino acid peptide originally characterized as a neuropeptide derived from the pituitary gland. α-MSH is synthesized from pro-opiomelanocortin (POMC) by the action of specific prohormone convertases and is involved in the regulation of important physiological functions including food intake, energy homeostasis, modulation of immune responses and photoprotection.

<p>Bachem ID: 4014443.</p>

DL-APNE (or NAPNE), a chromogenic substrate for chymotrypsin and microbial serine proteases, e.g. subtilisin. It is also hydrolyzed by cathepsin G. NAPNE was used by Yakoby and Raskin to determine the inhibitory activity of trypsin and chymotrypsin.

<p>Bachem ID: 4096166.</p>

Impurity of tetracosactide, which is a synthetic peptide analog of the human adrenocorticotropic hormone that stimulates the production of cortisol.

Chemotactic peptide antagonist.

Chromogenic substrate for dipeptidyl aminopeptidase II (DPPII), also cleaved by a dipeptidyl peptidase V (DPP V) from Aspergillus fumigatus.

Substrate for urokinase.

Ac-WEHD-CHO, a very potent reversible inhibitor of caspase-1 (ICE). It bears the optimal tetrapeptide recognition motif for this enzyme. With a Ki of 56 pM it belongs to the most potent reversible, peptide-based inhibitors described for any protease. For caspase-8 a Ki of 21.1 nM has been reported.

This enzyme substrate was used to test the concept of substrate-assisted catalysis with an engineered bacterial serine endopeptidase, subtilisin. Suc-FAAF-pNA has been employed for assaying subtilisins from psychrophilic bacteria and myroilysin, a metalloproteinase from the deep sea bacterium Myroides profundi.

ACTH (1–14) is a fragment of the ACTH hormone, which stimulates the adrenal cortex and the secretion of glucocorticoids such as cortisol. ACTH (1–14) is an agonist of the melanocortin-1 and 3 receptor (K1 = 0.836 ± 0.33 and 48,3 ± 9,0 nmol/L respectively).

Competitive inhibitor of acyl peptide hydrolase.

Short-term administration of deslorelin stimulates the formation of LH and FSH, which induce an increase in the production of testosterone and estradiol. Prolonged administration of the GnRH agonist causes a sustained down-regulation of circulating LH and FSH levels and hence suppression of steroidogenesis.

The orphan G protein-coupled receptor APJ has been shown to be a coreceptor for human and simian immunodeficiency virus (HIV and SIV) strains. As long as apelin is an endogenous ligand for the APJ receptor, inhibitory effects of apelin peptides on HIV infection have been examined and it has been found that the apelin peptides inhibit the entry of some HIV-1 and HIV-2 strains into NP-2/CD4 cells expressing APJ. For apelin-36 the strongest inhibitory efficiency has been reported.

Substrate for leucine aminopeptidase.

N-terminal sequence of dynorphin A and the neoendorphins.

Nafarelin is a synthetic decapeptide agonist of the luteinizing hormone-releasing hormone (LHRH) which is approximately 200 times more potent than the natural peptide. Like LHRH nafarelin stimulates the release of the gonadotrophins luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary which in turn results in an initial increase of testosterone and estradiol synthesis. Continuous administration of LHRH or one of its analogs causes a sustained down-regulation of circulating LH and FSH levels leading to a suppression of testicular and ovarian steroidogenesis. Currently, nafarelin is indicated for the treatment of endometriosis and for the use in reproductive medicine. CAS Number (nafarelin acetate): 86220-42-0.

Suc-AAPL-pNA, a sensitive substrate for human and especially porcine pancreatic elastases. Substrate for leucine endopeptidase from the psychrotropic bacillus B. cereus.

A ghrelin receptor antagonist. Asakawa et al. found that peripherally administered (D-Lys³)-GHRP-6 (HwkWfK-amide) decreased food intake in lean mice, in mice with diet induced obesity, and in ob/ob obese mice, and that repeated administration of this GHS-R antagonist decreased body weight gain and improved glycaemic control in ob/ob obese mice.

RR-AMC, fluorogenic substrate for dipeptidyl peptidase III (DPP III).

AAF-AMC, fluorogenic substrate for tripeptidyl peptidases I and II and for tripeptide aminopeptidase EC 3.4.11.4.

Active molecules as peptides can be readily conjugated to this cell-permeable peptide by the mercapto moiety.

Suc-AAVA-pNA has been used for assaying hamster chymase 2.

Substrate for aminopeptidase M and leucine aminopeptidase.

Human ghrelin (GHR), the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), potently stimulates GH release. The Ser³ octanoyl ester turned out to be essential for generating this activity. Ghrelin plays an important role in the short-time regulation of appetite and in the long-time regulation of energy balance and glucose homeostasis. A number of studies showed that ghrelin is also involved in the regulation of gastrointestinal, cardiovascular, and immune functions as well as in bone metabolism.

In contrast to the octanoylated peptide, the non-acylated ghrelin does not activate growth hormone secretagogue receptor-expressing cells. The peptide decreases food intake and gastroduodenal motility in conscious rats, probably by crossing the blood-brain barrier and activating the brain receptor directly.

Fluorogenic substrate for farnesyl diphosphate farnesyltransferase (FTase). The pentapeptide is based on the C-terminal region of H-Ras with a dansyl group attached to the N-terminus. Due to farnesylation of the cysteine thiol group the dansyl group is placed from a polar to a non-polar molecular environment which is accompanied by an enhancement of fluorescence and a shift to a lower wavelength emission maximum of the dansyl group. Complete conversion of the product results in a decrease of the emission maximum wavelength from 565 nm to 515 nm together with a 13-fold enhancement in fluorescence intensity at 505 nm. Dansyl-GCVLS can be used for continuously monitoring FTase activity in the presence of farnesyl diphosphate (FPP) at 505 nm using an excitation wavelength of 340 nm (kcat = 0.5 s⁻¹; Km = 1.4 µM). It represents a useful tool for screening potential FTase inhibitors. The substrate is highly specific to FTase and is not recognized by geranylgeranyl transferse type I (GGTase I). Concentrations of stock solutions of Dns-GCVLS can be calculated from the extinction coefficient of the dansyl moiety (ε₃₄₀ = 4250 M⁻¹cm⁻¹ in 20 mM Tris-HCl, pH 7.5, 10 mM EDTA).

CTAP, an analog of CTOP, is a selective µ-opioid receptor antagonist.