Peptide Services

Services & Products

Custom Peptide Synthesis, Custom Antibody Service, Catalog Peptides.

Peptide Services

Rush Peptide Service
Custom Peptide Synthesis
Peptide Library Service
Peptide Conjugation Service
Antibody Service
Custom Chemical Synthesis

Custom Peptide Synthesis

Phosphorylated peptides; Citrullinated peptides; Succinylated peptides; Acetylated peptides; Amidated peptides; PEGylated peptides; Fluorescent peptides; Biotinylated peptides; Stable Isotope labeled peptides; Cyclic peptides; Stapled peptides; Branched Peptides; Metal Chelator peptides.

How it work?

Peptide Amounts from mg to kg
Peptide of 2-120 Amino Acids
Purity of All Levels
Comprehensive Modifications
Peptide Conjugations

Rush Peptide Synthesis in 3-5 Days!

Please specify that your orders are for RUSH synthesis when ordering. Rush fee applies.

InnoPep provides the fastest turnaround time and most reliable quality for the life science research community. Peptides are made in San Diego, USA. Projects move from conception to bench in only 3–5 days so you can deal with your research deadlines.

Please specify that your orders are for RUSH synthesis when ordering. Our standard synthesis service, with its regular turnaround time of 2–3 weeks, is assumed unless the customer states otherwise.

Optional Local Pickup: Please contact us if you would like to pick up your peptides from our San Diego lab.

Peptides

Peptide phosphorylation is a peptide containing phosphate (PO43-) group to a peptide containing serine, threonine or tyrosine. Phosphorylation is one of important post-translational modifications (PTMs) of protein function. Protein phosphorylation can occur on several amino acids.

Phospho-specific antibody generated by using phosphorylated peptide are commonly used to detect whether a protein is phosphorylated at a particular site. We offer peptide phosphorylation synthesis on pSer, pTyr, pThr or D-pSer, D-pTyr, D-pThr. We can also place phosphorylation site at multiple positions.

Citrullination is a post translational modification, where Arginine is deaminated to form Citrulline. The production of Citrulline containing peptides is a fairly straight forward process. They can be made at high purity, and we have provided quite a few of these over the years.

Succinylation is a newly discovered protein post-translational modification (PTM), where a succinyl group (-CO-CH2-CH2-CO-) is added to form succinyl lysine (Ksucc). This novel PTM has been identified in both histone and non-histone proteins. Its distinct biological role is yet to be determined. As it i) changes the charge of lysine residue, ii) results in a bulky moiety, compared with canonical PTMs (e.g. acetylation or methylation), Ksucc is postulated to be substantially involved in protein functionality and cellular signaling network.

Pegylation plays an important role in drug delivery, enhancing the potentials of proteins and peptides as therapeutic agents. Pegylation is the process of linking one or more repeating chains of ethylene oxide (CH2CH2O)x to a therapeutic peptide or protein. Pegylated derivatives can improve the therapeutic properties by improving the pharmacokinetics (solubility, stability, absorption, biopharmaceutical actions) and the pharmacodynamics (immunogenicity, antigenicity, proteolysis) profiles.

Fluorescence labeled peptides are commonly used for protein binding or localization studies. These labels can be incorporated at many positions in the peptide. Frequently, they are incorporated at the N-terminus or at Cys/Lys side chains.

Biotinylation of peptides can be performed either at the N- or C-terminus. Biotinylation at the N-terminus can be performed directly to the primary-terminal amino group, whereas biotinylation is usually performed at the side-chain of lysine. An important consideration when making a biotinylated peptide is to ensure there is a sufficient spacer arm between the biotin group and the amino acids in the peptide which are expected to interact with a macromolecule (such as an antibody). To avoid steric hindrance, a linker can be inserted between biotin and the peptide sequence. A hydrophobic straight chain spacer such as the 6-carbon ε-aminocaproic (Ahx) is frequently applied or a hydrophilic tetrapeptide such as -SGSG- can be inserted.

Peptide cyclization is a frequently used strategy for the development of peptides with enhanced conformational stability (compared to their linear analogs). Cyclic peptides metabolize slower due to their higher resistance toward proteases. They can be used to mimic the structure of biological active peptides (e.g peptide hormones).

Depending on the cyclization site, there are several methods to synthesize cyclic peptides, e.g. head-to-tail, side-chain-to-side-chain, head-to-side-chain, and side-chain-to-tail (see figure below). While head-to-tail cycles are usually formed by amide bond formation, side-chain-to-side-chain cycles are most often synthesized via Cys-Cys or amide bond formation.

Isotope labeled or heavy amino acids are derived from natural amino acids by substitution of atoms with respective heavy isotopes. The most frequent substitutions of non-radioactive amino acids are 12C by 13C, of 14N by 15N, and of 1H by 2H (deuterium).

Isotope labeled peptides share the same physiochemical properties and (apart from a few exceptions) the same chemical reactivity with their non-labeled counterparts. However, under certain conditions labeled and unlabeled peptides behave differently. This is the basis for the use of stable isotope labeled peptides in a variety of applications, e.g.

Reference material for mass spectrometry experiments (proteomics)
NMR studies (e.g. solution structure determination)
Reference material for pharmacokinetic analyses
Metabolite identification

These stable isotopic heavy peptides are synthesized using the Fmoc solid-phase peptide technology in our state-of-the-art peptide lab. The table below lists the most common stable isotopically labeled amino acids.

Branched peptides such as Multiple Antigen Peptides (MAPs) were invented in the 80s by Tam [Tam, J.P., (1998) Proc. Natl. Acad. Sci. USA, 85, 5409] and have been extensively tested to reproduce single epitopes to stimulate the immune system for new vaccine discovery. Also have found utility in antibody generation and siRNA delivery. We can synthesize peptides with up to 8 branches.

Molecular imaging has become an indispensable tool in modern diagnostics in biomedical research and therapeutic fields. Modern imaging techniques increasingly rely on the use of radioactive isotopes of certain metal ions, often in combination with targeting peptides.

The modifications can be made at the N-terminus or at the C-terminus via a C-terminal lysine. These conjugates are able to give very stable complexes of many metals or with radioactive isotopes of metals currently used in Nuclear Medicine (In-111, Y-90,Tc-99m, Lu-177, Ga-68).

We routinely synthesize a variety of metal chelating peptides, such as DOTA-, DTPA-, and NOTA-coupled peptides.

Disulﬁde-rich, bioactive macromolecules are widely represented in nature. Disulﬁde bonds stabilize higher-order structures that confer much enhanced chemical, biophysical, and metabolic stability. These higher-order structures are also integral to high potency and speciﬁcity in biological action, with conotoxins, epidermal growth factors, and the insulin superfamily peptides representing prominent examples.

Synthetic access to these peptides is essential to enable investigation of their structure−activity relationships and subsequent evaluation as drug candidates.

We applied and optimized the use of a series of different cysteine-protective groups (i.e. StBu, STmp, Trt, Mmt, Acm, tBu, etc.) that allow for a sequentially directed disulfide bond strategy (up to 4 different SS-bonds).

Stapled Peptides

Peptide-based therapeutics offer a viable solution since they are known to be potent and selective against biological targets that are otherwise difficult to manipulate with small molecules. Such approaches have been used to manipulate intracellular protein-protein interactions (PPIs), wherein large and shallow contact areas of a protein are successfully targeted by peptides, which are able to mimic the native counter protein. Although highly potent and selective, peptides often suffer from poor cell permeability, plasma stability and hence poor bioavailability. To overcome the poor pharmacokinetic properties of linear peptides, stapled peptides have been successfully developed and used to target intracellular PPIs. Indeed, an all-hydrocarbon stapled peptide, ALRN-6924, is under clinical development as an anti-cancer drug targeting HDM2/p53.

Different stapling chemistries have strengths and weaknesses in terms of both their synthetic ease and potential utility for addressing biological questions. To facilitate our clients’ research and project development, InnoPep is able to provide a comprehensive list of stapled peptides synthesis services, which includes: ring-closing metathesis, lactamization, click chemistry, and thioether formation.

The all-hydrocarbon a-helix staple combines two distinct conformational stabilization strategies to induce a-helical structure, namely, a,a-disubstitution and macrocyclic bridge formation. Three different types of all hydrocarbon staples are shown in the figure, demonstrating the creation of a stabilized α-helix in a peptide. Approximately one turn of the helix would be i and i+3 (or i, i+4) and two turns of the helix would be i, i+7; three turns of the helix would be i, i+11. During solid-phase peptide synthesis, a-methyl, a-alkenylglycine cross-linking amino acids are incorporated in appropriate positions. An i, i+3 stapled peptide requires one unit of R5 at the i position and one unit of S5 at the i+3 position. An i, i+4 stapled peptide requires two units of S5 incorporated at the relative positions i and i+4. An i, i+7 stapled peptide requires one unit of R8 at the i position and one unit of S5 at the i+7 position. Resin-bound peptide is treated with Grubbs I olefin metathesis catalyst to produce a cross-link between the two non-natural amino acids, resulting in a stapled peptide that is braced in a a-helical conformation.

The high efficiency and mild conditions of “click” reaction (Copper catalyzed Huisgen 1,3-dipolar cycloaddition reaction) combined with the ease of synthesis of the necessary unnatural amino acids allows for facile synthesis of triazole-stapled peptides. For example, a combination of L-Nle(εN3) and D-Pra (D-Propargylalanine) substituted at the i and i+4 positions can be used for the generation of single triazole-stapled peptides.

Advantages of Stapled Peptides

Better target affinity
Increased proteolytic resistance and serum half-life
Cell penetration through endocytic vesicle trafficking
Target either extracellular or intracellular proteins
Disrupt Protein-Protein interactions
Non-immunogenic
Viable pharmacokinetics and in vivo stability

Stapled peptides have been studied in the targeting of several proteins which are relevant in Cancer, Diabetes, HIV, Atherosclerosis etc. These include proteins such as BCL-2, BCL-XL, BAX, MCL-1, glucokinase, hDM2, hDMX, NOTCH/CSL, HIV-1 capsid, HIV-1 gp41, ABCA1 and Estrogen receptor.

References

Jackson DY, King DS, Chmielewski J, Singh S, & Schultz PG (1991) General approach to the synthesis of short alpha-helical peptides. J. Am. Chem. Soc. 113(24):9391-9392.
Walensky LD, et al. (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305(5689):1466-1470.
Chang YS, et al. (2013) Stapled alpha-helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proc. Natl. Acad. Sci. U. S. A. 110(36):E3445-E3454.
Walensky LD & Bird GH (2014) Hydrocarbon-stapled peptides: principles, practice, and progress. J. Med. Chem. 57(15):6275-6288.

Glycopeptides, especially the glycan chains, have played pivotal roles in various biological activities and involved in numerous biological recognition events, such as immune system, endocrine system, protein folding and cell communication. Due to the natural linkage between glycan and the amino acid residues of peptide, glycopeptides can be classified into two principal types: N-linked and O-linked glycopeptides.

N-linked glycopeptides

N-linked glycosylated peptides are the most frequently found glycopeptides
They contain an amide bond between a glycan and the side chain of Asp, the so-called N-glycosidic bond
The sites of N-glycosylation in N-glycoproteins are characterized by sequons Asn-Xaa-Ser/Thr (NXS/T, where Xaa is any amino acid except proline).
The carbohydrate moiety is more variable, including alpha- and beta-Glc and beta-N-acetylgalactosamine (GalNAc)

O-linked glycopeptides

O-linked glycoproteins are far more diversified than N-glycoproteins
Most abundant is the mucin-type with an alpha-linkage between GalNAc and serine or threonine
Examples of other saccharides linked to serine and threonine include alpha-galactose (Gal), glucose (Glc), fucose (Fuc), mannose (Man) and Xylose (Xyl)
A separate class of O-linked glycosylation, which appears to be functionally distinct, is the O-GlcNAc modification found as monosaccharides attached to either Ser or Thr

Glycoslyation of peptides has been an effective synthetic strategy to improve metabolic stability and enhance drug delivery. Glyco-amino acids used in solid phase peptide synthesis are Fmoc protected with the sugar generally protected as the fully acetylated form.

A selection of glycosylated amino acids that have been successfully incorporated into glycopeptides at InnoPep is shown below. Please contact us for your specific request.

References

Rudd PM, et al. (2001) Glycosylation and the immune system. Science. 291(5512):2370-2376.
Carganico S, et al. (2009) Building blocks for the synthesis of post-translationally modified glycated peptides and proteins. J. Pep. Sci. 15(2):67-71.
Yamamoto T, et al. (2009) Improving metabolic stability by glycosylation: bifunctional peptide derivatives that are opioid receptor agonists and neurokinin 1 receptor antagonists. J. Med.
Chem. 52(16):5164-5175.
Moradi SV, et al. (2016) Glycosylation, an effective synthetic strategy to improve the bioavailability of therapeutic peptides. Chem. Sci. 7(4):2492-2500.

Proteins can be post-translationally modified in many different ways, and a common post-transcriptional modification of lysine involves methylation. Lysine can be methylated once, twice, or three times by lysine methyltransferases. The transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as histone methyltransferases (HMTs).

Histone lysine methylation occurs on histones H3 and H4, and can signal either transcriptional activation or repression, depending on the sites of methylation. Methylation on the same site can also lead to different outcomes depending on the number of methyl groups added to lysine’s side chain. Histone methylation peptides of histone H3 and H4 include mono-methylated, di-methylated, and tri-methylated sequences. These epigenetic peptides are useful to researchers conducting studies in enzyme activity and screening inhibitors for specific HMTs.

With histone methylation playing critical roles in many epigenetic regulations, InnoPep is able to produce peptides with mono-, di- and tri-methylated Lys and Arg analogs listed.

References

Martin C & Zhang Y (2005) The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell Biol. 6(11):838-849.
Chatterjee J, Rechenmacher F, & Kessler H (2013) N-methylation of peptides and proteins: an important element for modulating biological functions. Angew. Chem. Int. Ed. Engl. 52(1):254-269.
Hamm CA & Coata FF (2015) Epigenomes as therapeutic targets. Pharmacol. Ther. 151:72-86.

Shopping Cart

Services & Products