CJC 1295 is a synthetic version of hormone releasing factor GRF which has been modified to include Gin, D-ala, Ala and Leu substitutions that can be found at positions 27, 15, 8 and 2. These allow the peptide to take on more stability.
Specifically, the substitution as position 2 can prevent DPP-IV cleavage while the alteration at position 8 can reduce asparagne rearrangement of the aspartic acid and amide hydrolysis. The alteration at position 15 enhances the bioactivity of the peptide; the substitution at position 27 was designed to prevent methionine oxidation.
CJC 1295 was designed to create a long acting GHRH. GHRH contains 44 amino acid peptide hormones that are produced in the hypothalamus and used by an animal’s body to create arcuate nucleus reactions. GHRH can be used to stimulate the pituitary gland to encourage hormone secretions as well. GHRH is released in pulses which will, in turn, encourage pulses of hormone and slow wave sleep.
Effects of Mild Hypthermia
Studies have suggested that mild hyperthermia that is induced during hemorrhagic shock can be beneficial, which confirms an investigations into the mechanisms of proinflammatory cytokines.
Cytokines can mediate multiple organ failure after a hemorrhagic shock or resuscitation. It was hypothesized that mild hypothermia could improve the chances of survival of an animal due to the mild anti-inflammatory effects this was caused.
Mild hypothermia was induced by withdrawing blood from a rat’s tail and then hyposensitive fluid resuscitation decreased below 40mmHg, starting at 30 minutes and continuing through 90 minutes.
At 60 minutes the hypothermia groups saw an increase of the baseline survival while the untreated groups did not see this increase.
The hypothermia groups also save an increase in the peptide reaction after uncontrolled hypothermia. This induced a pro-inflammatory cytokine response which indicates that unexpected increases of TNF with hypothermia should be investigated further.
Potential Anti-HIV Activity
Clinical applications of peptide chemicals is often limited due to their short half lived in vivo and their potential immunogenicity.
Frequently injecting peptides has been shown to create treatment challenges for chronic diseases, including HIV. Chemically modifying peptides for HIV fusion with an 3-maleimidopropionic acid allows for irreversible conjugation with albumin serums at a 1:1 ratio.
Modifying FBoo6M with this modification at amino acid 13 can quickly conjugate an albumin reaction with an intravenous injection, rapidly extending the half-life in vivo.
This alteration shows a significant inhibitory activity against a number of isolates in vitro and in vivo. There were no immunogenicity/antibody formations detected after this application. Applying this similar alteration to peptides, including CJC 1295, could significantly improve their half-life, allowing for a wider range of applications.
Activating GRF Receptors in the Anterior Pituitary
The bioconjugatoin of free thiol on the cys34 serum albumin in vivo may be helpful in extending the half-life of peptides that affect the plasma.
Human serum albumin conjugates showed an enhanced stability from dipeptideylpeptidase-IV and maintained their bioactivity in hormone secretion assayed in cultured anterior pituitary cells cultured from rats.
CJC1295 proved to be the best solution, creating four times the hormone increase over two hours compared to hGRF 1-29.
The presence of CJC 1295 corresponded to the increase of serum albumin after 15 minutes and this circulation continued for 24 hours after this administration.
Active portions of GRF and GHRH peptides can be found in a 29 peptide amino acid chain, known as GHRH1-29. This also causes pulsatile releases of peptides, by causing a negative feedback loop in portions of the hGH axis controls that the body produces to encourage homeostasis. Research focuses on the ability of CJC 1295 to produce similar results.