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Large Scale Custom Peptide Synthesis

Synthetic peptides have proven to be very valuable in most biomedical laboratories; since the mid-60’s to the present, biologically active peptides have been integrated into the growing number of API’s (active pharmaceutical ingredients) and also as stand alone products such as Vasopressin, Gonadorelin, Leuprolide, Goserelin.among others. With the completion of the human genome, and the confirmation of about 30,000 proteins produced in the human body, there are now many more targets for biomedical researcher to explore.

Generally biomedical researchers will explore possibilitis how to increase the native potency of a given peptide/protein, for example, by rationale design. Often only small amounts of peptides are needed, more likely in the milligram scale. However, once a desired activity or potency is found, a larger scale of synthesis is need, usually in the gram to grams scale, in order to initiate small animal studies. Upon successful validation, even larger scale synthesis is needed, ranging from hundreds of grams to multikilo amounts. Bio-Synthesis has over 32 years of experience in custom synthesis, from research grade scale to multikilo amounts.

Large scale peptide synthesis can be carried out either in solution or in solid phase. Generally peptides shorter than 8 amino acids are prepared by solution chemistry, as it is usually more economical to do so. Peptides larger than 8 residues are generally assembled by solid phase chemistry. Commercially peptides are produced up to about 50 residues in length, however, once a pilot run is established and it is determined that a high load resin can be used for the synthesis (about 1 mmmol/gram) high yields can be obtained for short peptides (8-20). Above 20 residues a good balance needs to be found between resin loading and possible steric hindrance during synthesis to achive good results. Solid phase synthesis can be carried out either in a fully automated fashion or manually. On the other hand manual synthesis for short peptides has the advantage of being able to scale up with a more flexible approach. Troubleshooting of unexpected problems may aslo be easier. For example, the operator can wash away piperidine during Fmoc deprotection, in the event of power failure or machine troubles which can be the case for automated instruments. Also the thermodynamic mixing can be better controlled in manual systems. We are not saying that manual systems are better, we are saying that for shorter and multikilo (10-20 kgs runs) solid manual methods are a good alternative. Large scale fully automated peptide instruments, have the obvious advantage of unattended operation and extensive documentation and for longer and mid-scale synthesis provide a generally reliable venue.

Large scale peptide synthesis manufactured following GMP guidelines will include the following documentation, as part of the quality control assays:

MS for Identity

± 1 amu.

RP-HPLC for purity 

³95%,

AAA for Identity

± 15% of theory

Nitrogen analysis for peptide content

Report Results

Karl Fischer for water content

Report Results

Residual solvents test

ICH/USP limits

Quantification of Counter Ion

Report Results

Bacterial Endotoxin, LAL test

≤ 0.25 EU / mg

Bioburden

≤ 10 CFU / 100 mg

Mass balance 

90-105%

Bio-Synthesis has been producing synthetic peptides for over 32 years. Our expertise in custom synthetic polypeptide manufacturing allows us to produce synthetic peptides with high-quality and on a large-scale with the highest success rate demonstrated by our long standing records. We have been delivered more than 150,000 peptides to customers worldwide, including very hydrophobic polypeptides, peptides with multiple disulfide bonds, multi-phosphorylated peptides as well as extremely long peptides. Our large scale non-GMP synthesis can deliver 5 kilograms of peptides during a single synthesis run and we have the capacity to synthesis >10,000 peptides per month.

Whenever your research work may require large scale synthesis of peptides, please keep us in mind, Bio-Synthesis Inc. staff will be glad to help you achieve your research/production goals.