C peptide

Elber et al. [48] applied this method to explore the dynamics of the C-peptide in water with impressive results. More than 30 trajectories of C-peptide were generated, and the process of helix fonnation in water was examined. Remarkably, a time step of 500 ps was used, which allowed for the study of peptide folding on extended time scales. 

Harrison, S.C. Peptide-surface association the case of PDZ and PTB domains. Cell 86 341-343, 1996. 

Fig. 1.9 S urface pressure ( r)-area (A) isotherms obtained for a lipid mixture (DPPC POPG PA, 68 22 9 (by weight)), alone and with 10% (w/w) of either SP-C peptide or SP-C peptoid added. Results indicate that the addition of the SP-C mimics engenders biomimetic surface activity, as indicated by lift-off at a higher molecular area and the introduction of a plateau...

Fig. 19 Lateral model for assembly of peptide mixtures producing laminated P-sheets. Residues in solid circles are on the upper face, residues in dashed circles are on the lower face of the P-sheeL Reproduced from Takahashi et al. [57] with permission. Copyright Wiley-VCH. Numbers refer to the peptide entries in Fig. 18. Arrows are directions of the (antiparallel) beta sheet strands beginning and end of arrow correspond to N- and C-peptide termini respectively...

Fig. 35 TEM image of peptide fibres coated with streptavidin-gold nanoparticles, (a, b) Peptides with biotin directly attached (using SAF-pl-biotin) particles are 10 nm, (c) Peptide fibre with biotinylated anti-FLAG antibody attached that was then bound to gold-labelled streptavidin particles are 5 nm. Reprinted with permission from Ryadnov and Woolfson [76]. Copyright 2004 American Chemical Society...

Figure 42-2. Chemical diversity of hormones. A. Cholesterol derivatives. B. Tyrosine derivatives. C. Peptides of various sizes D. Glycoproteins (TSH, FSH, LH) with common a subunits and unique P subunits.

Figure 42-12. Structure of human proinsulin. Insulin and C-peptide molecules are connected at two sites by dipeptide links. An initial cleavage by a trypsin-like enzyme (open arrows) followed by several cleavages by a car-boxypeptidase-like enzyme (solid arrows) results in the production of the heterodimeric (AB) insulin molecule (light blue) and the C-peptide.

The human pancreas secretes about 40—50 units of insulin daily, which represents about 15—20% of the hormone stored in the B cells. Insidin and the C-peptide (see Figure 42—12) are normally secreted in equimolar amounts. Stimuh such as glucose, which provokes insidin secretion, therefore trigger the processing of proinsidin to insidin as an essential part of the secretory response. 

It has been suggested that the easiest way to differentiate between type 1 and type 2 DM is by measuring C-peptide levels. Type 1 diabetics have C-peptide levels below 1 ng/mL (0.33 nmol/L), whereas those with type 2 disease will have values greater than 1 ng/mL (0.33 nmol/L). 

Pancreas Fever, graft tenderness and swelling, abdominal pain, ileus, malaise Increased FBS, leukocytosis, decreased human C-peptide and urinary amylase levels... 

Bierzynski, Kim PS, Baldwin RL (1982) A salt bridge stabilizes the helix formed by isolated C-peptide of RNase A. Proc Natl Acad Sci USA 79 2470-2474. 

Osterhout JJ Jr, Baldwin RL, York EJ, Stewart JM, Dyson HJ, Wright PE (1989) 11 NMR studies of the solution conformations of an analogue of the C-peptide of ribonuclease A. Biochemistry 28 7059-7064. 

Shoemaker KR, Fairman R, Schultz DA, Robertson AD, York EJ, Stewart JM, Baldwin RL (1990) Side-chain interactions in the C-peptide helix Phe8-Hisl2+. Biopolymers 29 1-11. 

G Gwinup, AN Elias, ES Domurat. Insulin and C-peptide levels following oral administration of insulin in intestinal-enzyme protected capsules. Gen Pharmacol 22 143-246, 1991. 

Elber, R. Meller, J. Olender, R., Stochastic path approach to compute atomically detailed trajectories application to the folding of C peptide, J. Phys. Chem. B 1999, 103, 899-911... 

Bendayan, M. (1989) Ultrastructural localization of insulin and C-peptide antigenic sites in rat pancreatic B cell obtained by applying the quantitative high-resolution protein A-gold approach. Am. J. Anat. 185, 205-216. 

Figure 8.10 DNA and potentially information-bearing oligonucleotide analogues (a) DNA (b) pyranosyl analogue of RNA (c) peptide nucleic acid, PNA...

Proinsulin is proteolytically processed in the coated secretory granules, yielding mature insulin and a 34-amino acid connecting peptide (C peptide, Figure 11.1). The C peptide is further proteolytically modified by removal of a dipeptide from each of its ends. The secretory granules thus contain low levels of proinsulin, C peptide and proteases, in addition to insulin itself. The insulin is stored in the form of a characteristic zinc-insulin hexamer, consisting of six molecules of insulin stabilized by two zinc atoms. 

Although a high degree of homology is evident between insulins from various species, the same is not true for proinsulins, as the C peptide sequence can vary considerably. This has therapeutic implications, as the presence of proinsulin in animal-derived insulin preparations can potentially elicit an immune response in humans. 

An alternative method (developed in the Eli Lilly research laboratories), entails inserting a nucleotide sequence coding for human proinsulin into recombinant E. coli. This is followed by purification of the expressed proinsulin and subsequent proteolytic excision of the C peptide in vitro. This approach has become more popular, largely due to the requirement for a single fermentation and subsequent purification scheme. Such preparations have been termed human insulin prb ... 

Reubi, J. C. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocrinol. Rev. 24 389MZ7,2003. 

The average Mr weights were calculated using Biolynx (Micromass). c Peptides submitted to Edman degradation. 

P cells of the pancreatic islets in combination with atoms of zinc, but when required to regulate blood glucose concentration, the prohormone is cleaved and functional insulin is released into the circulation along with the C-peptide. This example of post-translational processing is mediated by peptidases which are contained in the vesicles along with the proinsulin. The fusion of the secretory vesicles with the cell membrane and activation of the peptidase prior to exocytosis of the insulin are prompted by an influx of calcium ions into the P-cell in response to the appropriate stimulus. Similarly, catecholamines are synthesized and held within the cell by attachment to proteins called chromogranins. 

Structurally insulin is a small peptide, with a molecular mass of around 5500 and composed of two subunits, denoted a and (3 chains. Insulin is synthesized as a single peptide, Proinsulin and stored within the pancreatic p-cells. At the moment of secretion, pro-insulin is cleaved, releasing C-peptide and functional insulin in to the blood circulation (Figure 4.22). 

Figure 4.22 Insulin is produced from pro insulin by proteolysis. Active hormone and inactive C-peptide are co-secreted...

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