Peptides injectables

Brown MR, Gray TS (1988) Peptide injections into the amygdala of concious rats effects on blood pressure, heart rate and plasma catecholamines. Reg Peptides 27 95-106. 

Cetin F, Dincer S (2007) The effect of intrahippocampal beta amyloid (1 2) peptide injection on oxidant and antioxidant status in rat brain. Ann N Y Acad Sd 1100 510-517... 

Potency relative to methionine enkephalin receptor affinities obtained by binding studies with 3H-naloxone analgesic carried out in rats following peptide injection into brain periaqueductal gray matter. b The terminal carboxyl group is reduced to an alcohol function. c The sulfur atom of methionine is oxidized to sulfoxide ... 

Figure 6. Comparison of the serum antibody levels at various times following inoculation with a synthetic peptide injected alone or in the presence of adjuvant. Synthetic peptide delivered (1) intranasally and covalently coupled to Pam3Cys (2) intraperitoneally and covalently coupled to Pam3Cys (3) intraperitoneally emulsified in CFA (4) intraperitoneally and covalently coupled to two palmitic acid molecules (S) intraperitoneally and covalently coupled to a cholesterol molecule (6) intraperitoneally in normal saline. The arrows indicate the times of immunisation. The right hand side of the figure is a representation of the structure of the synthetic peptide with Pam3Cys attached at the N-terminus. The three palmitic acid residues of the Pam3Cys moiety are seen at the bottom of the model.

The posterior lobe of the pituitary, ie, the neurohypophysis, is under direct nervous control (1), unlike most other endocrine organs. The hormones stored in this gland are formed in hypothalamic nerve cells but pass through nerve stalks into the posterior pituitary. As early as 1895 it was found that pituitrin [50-57-7] an extract of the posterior lobe, raises blood pressure when injected (2), and that Pitocin [50-56-6] (Parke-Davis) causes contractions of smooth muscle, especially in the utems (3). Isolation of the active materials involved in these extracts is the result of work from several laboratories. Several highly active posterior pituitary extracts have been discovered (4), and it has been deterrnined that their biological activities result from peptide hormones, ie, low molecular weight substances not covalendy linked to proteins (qv) (5). 

One of the early vaccine candidates was directed against sporo2oites, the form of the parasites that is first injected into the host by a mosquito. With recent development of recombinant techniques, several circumsporo2oite proteins or its related peptides were proposed as the vaccine candidates. Clinical trials have been carried out. The vaccines were immunogenic, but did not provide sufficient protective efficacy (90,91). 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

Fig. 3-3. Comparison of the values of enantiomeric resolution of different DNP-D,L-amino acids at different deconvolution stages of a cyclic hexapeptide sublibrary. Resolution values in a cyclo(Arg-Lys-X-X-X-P-Ala) sublibrary, in the first line, are compared to those obtained in sublibraries with a progressively increasing number of defined positions. All the sublibraries were 30 mM in the running buffer while the completely defined cyclo(Arg-Lys-Tyr-P-Tyr-P-Ala) peptide is used at 10 mM concentration. Conditions cyclopeptide sublibrary in 20 mM sodium phosphate buffer, pH 7.0 capillary, 50 pm i.d., 65 cm total length, 57 cm to the window V = -20 kV, I = 40 electrokinetic injection, -10 kV, 3 s detection at 340 nm. (Reprinted with permission from ref. [75]. Copyright 1998, American Chemical Society.)...

Hormones, peptides and neurotransmitters Effect of ICV injection on food intake Effect of gene deletion on food intake Response to adiposity signals Receptor Effect of receptor defect on food intake... 

CART (cocaine- and amphetamine-regulated transcript) is a hypothalamic peptide that inhibits both normal and starvation-induced feeding when injected into cerebral ventricles of rats. CART is co-localized with the anorexigenic peptide a-melanocyte-stimulating hormone in neurons of the arcuate nucleus. Secretion of CART is stimulated by leptin and CART may be an endogenous inhibitor of food intake. 

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

McMahon B.M., Stewart J.A., Bitner M.D., Fauq a., McCormick D.)., Rich elson E. Peptide nucleic acids specifically cause antigene effects in vivo by systemic injection. Life Sci. 2002 71 325-337. 

FIGURE 14 Pharmacokinetics of P-18-liposorae injected subcutaneously. Liposomes containing peptide hormone with... 

Hymenoptera venoms are composed of biogenic amines and other low molecular weight substances, of basic peptides and of proteins. Injection of venom by Hymenoptera stings has toxic effects, due to biogenic amines, peptides and proteins biogenic amines such as histamine cause pain, are vasodilatory and increase... 

These two studies in particular are important. They demonstrate that not only can Pn peptide self-assembly be adjusted by sequence modification to suit a particular ionic strength and pH (e.g. conditions found in vitro or in vivo) but that it can be also made reversible and responsive. This raises the possibility that these peptides can be used in drug delivery, or as therapeutics that self-assemble post-injection. 

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