• Histone proteins and their role in chromatin organisation

    DISCOVERY peptide LL13-37 DISCOVERY peptides from Cambridge Research Biochemicals

    Histone proteins help compact and organise the DNA of the nucleus and provide it with structural support, they also play key roles in orchestrating gene expression. The four core histones, H2A, H2B, H3 and H4 form a complex comprising an H3-H4 tetramer and two H2A-H2B dimers, known as the histone octamer core. Around this core, DNA is wound forming a DNA/histone complex known as the nucleosome. Between the nucleosome is the internucleosomal DNA which is stabilised by the linker histone H1.

    The tail region of the four core histones is able to undergo modifications such as acetylation, methylation, phosphorylation, citrullination, SUMOylation and ubiquitination. These modifications can alter the properties of the chromatin regions in which they occur. For example acetylation generally results in the more open euchromatin state which allows more active transcription such as in H4 K5Ac, K8Ac, K12Ac K16Ac fluorescently labelled peptide. Methylation generally has the opposite effect and results in more closed heterochromatin and transcriptional repression such as H3 K23 trimethylation which has been associated with meiotic cell divisions. Hypermethylation is also seen in some cancer cells and can result in unchecked cell growth.

    The modifications of core histones are carried out by histone modifying enzymes such as histone acetyltransferase (HATs) and histone deacetylases (HDACs), histone methyltransferases (HMTs) and lysine demethylases (KDMs) and kinases and phosphatases.  These histone modifications can occur in different complex combinations; making up what is known as the “histone code”.  Alterations in the histone modification patterns, often due to aberrant expression of histone modifying enzymes, have been seen in diseases such as cancers and autoimmune, cardiovascular and neurodegenerative disorders.

    In addition to these histone modifications, the four core histones can be replaced in certain cells by histone variants which can further alter the nature of the chromatin and affect its level of compaction. Examples of such variants include: histone H3.3, often associated with pericentromeric or telomeric regions for which we have also raised antibodieshistone H2AB1 which creates an unconventional chromatin structure associated with active transcription and; γH2Ax which is associated with DNA double strand breaks, such as during meiosis for which we have also raised an antibody.

    Here are some of our popular histone peptides and antibodies:

    Histone H2A:
    Histone H2A (1-20)-GGK(Biotin): crb1000863
    Histone H2A (78-86): crb1001395
    Histone H2AB1 (22-30) Light: crb1001329

    Histone H2B:
    Anti-Histone H2B antibody crb2005165

    Histone H3:
    Histone H3 (1-20) K4Me3, K9Ac, pS10-GG-[Lys(5- FAM)]: crb1101265
    Biotin-Histone H3 (14-34) pT22 K23Me3: crb1000344
    Histone H3 (20-36) K27Me2 Heavy: crb1300455

    Histone H4:
    Histone H4 (1-21) R3Me2: crb1000907
    Acetyl-Histone H4 (1-23) K5Ac, K8Ac, K12Ac, K16AcGG-[Lys(5-FAM)]: crb1101268
    H4 peptide (16-23):  crb1001167

    To discover our full histone peptides range please click here

    Visit Discovery Antibodies to view our range of histone antibodies

  • The role of β-Amyloid Peptides in Alzheimer's Disease

    Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. AD is characterised by progressive cognitive decline and memory dysfunction.   The two major histopathological lesions in AD are senile plaques composed of diverse beta-amyloid (Aβ) peptide aggregates and neurofibrillary tangles composed of tau proteins aggregates.  The dysregulation of Aβ production, folding, clearance and degradation result in the accumulation of Aβ and formation of senile plaques.  However, the correlation between Aβ plaques density and the severity of AD is ambiguous. Studies show that elevated levels of Aβ, oligomeric Aβ and protofibrils can induce calcium dyshomeostasis, trigger activation of caspase 3, or regulate a variety of signalling cascades (such as NMDARs and AMPARs) which lead to synapse dysfunction, shrinkage, collapse and neuronal cell death. It has been suggested that soluble nonfibrillar intermediates are the initiators of AD, whereas mature fibril formation represent the later stages of AD pathology.

    Amyloid precursor protein (APP) is sequentially cleaved by β- and γ-secretase to form Aβ peptides. β-secretase cleaves APP to release soluble APPβ and exposes a membrane bound C-terminal fragment (CTF99). Intramembrane proteolysis of CTF99 by γ-secretase initially occurs at various ε-cleavage sites, followed by carboxypeptidase cleavage at γ-cleavage sites to produce 39-43 amino acid Aβ peptide fragments. Aβ (1-40) is the most abundant form followed by Aβ (1-42). Aβ peptides undergo a conformation switch from α-helical to β-sheet structure. The Aβ β-sheets can adopt parallel or anti-parallel arrangements within protofilaments depending on the peptide properties. The β-sheet content is linked to Aβ insolubility. The longer forms of Aβ are more hydrophobic and fibrillogenic. Aβ (1-42) has been identified as the major component in senile plaques. An increase in Aβ (1-42) to Aβ (1-40) ratio has been shown to increase the propensity for Aβ aggregation. The fibrillar state has also been shown to be associated with protease resistance. The solubility and composition of Aβ species in different populations of amyloid deposits correlates to the disease state of the patient.

    Synthetic Aβ peptides are widely used to examine the structure, assembly and the activity of Aβ monomers, soluble oligomers and insoluble fibrils. Aβ peptides provide a means to assess the dynamics of nucleation and elongation of homogeneous and heterogeneous Aβ fibrils under various physiological conditions. Studies using Aβ peptides and their truncated variants provide an insight into biophysical properties and fibrillogenic regions and help identify intermediate species that contribute to Aβ toxicity. Furthermore, Aβ peptides are subject to post-translational modifications, such as oxidation, phosphorylation, isomerisation, nitration and glycosylation, which exhibit different physiological and pathological properties. Understanding the effects of various modifications will help establish factors that influence Aβ amyloidogenicity.

    Discover the amyloid peptides range

    Neurodegenerative Disease related peptides

    Other articles:

    When will there be a cure for Alzheimers Disease? an interview with Dr John Viles


  • Anti-Microbial Peptides: Focus on LL-37

    Cathelicidins form a distinct class of proteins that are key components of the innate and adaptive immune response. They also play a role in apoptosis, inflammation, phagocytosis and angiogenesis. The hallmark of the cathelicidin family of proteins is the presence of a highly conserved cathelin domain. Cathelicidins are expressed as inactive precursor proteins and their proteolytic cleavage leads to the release of active mature peptides ranging from 12 to 88 amino acids. The dominant mature cathelicidin antimicrobial peptide (CAMP) is LL-37 in humans, and cathelicidin-related antimicrobial peptide (CRAMP) in rodents.

    The LL-37 peptide is a 37-residue with two leucine residues at the N-terminus. LL-37 contains an N-terminal helical structure and a flexible C-terminal region. LL-37 belongs to the class of α-helical antimicrobial peptide (AMPs) and possesses amphipathic properties. The bioactive peptides exhibit a broad-spectrum of antimicrobial activity against bacteria, viruses, and fungi. LL-37 can interact with invading pathogens, permeabilise the membranes and subsequently neutralise the activities of endotoxins, such as lipopolysaccharide.

    Cathelicidin peptides can act directly and indirectly to regulate the activity of various cells in the immune system. LL-37 is a multifunctional signalling peptide that possesses various immunomodulatory activities. Depending on the environment and the stage of disease pathogenesis, LL-37 can exhibit both pro-and anti-inflammatory activity. A multitude of receptors recognize LL-37, where it can stabilize and trigger their activity and regulate downstream immunoregulatory mediators.  LL-37 can also induce cytokines and chemokines release and acts as a potent chemoattractant and an adjuvant.

    Available to order from our Discovery® catalogue:

    LL-37 acid (catalogue number: crb1000007)

    LL-37 amide (catalogue number: crb1000864)

    Labelled LL-37 peptides available soon

    Biotin-LL-37 (catalogue number: crb1000836)

    [5-FAM]-LL-37 (catalogue number: crb1000837)


    LL13-37 (catalogue number: crb1000034)

    LL17-29 (catalogue number: crb1000035)

    LL17-32 (catalogue number: crb1000036)


    CRAMP (1-39) (catalogue number: crb1000262)

  • 10% Discount On Your First DISCOVERY® Purchase

    We are offering a 10% discount off your first purchase from DISCOVERY® Peptides & Antibodiesusing the code : ENDEAVOUR10

    The code is valid across all products on the DISCOVERY® Peptides site and also on our sister site DISCOVERY® Antibodies.

  • Peptide Substrates: Insulysin FRET substrate [Mca]/[Dnp]

    Fluorescence Resonance Energy Transfer (FRET) peptides are convenient tools for the study of peptidase specificity and enzymatic activity. The Insulysin FRET substrate [Mca]/[Dnp] is a synthetic insulysin peptide substrate that contains an N-terminal fluorescent 7-methoxycoumarin (Mca) group and a C-terminal 2, 4-dinitrophenyl (Dnp) quencher; the FRET peptide exhibits internal fluorescence quenching when intact. Hydrolysis of a peptide bond between the donor/acceptor pair generates fluorescence, enabling the quantitative measure of enzymatic activity.

    Insulysin, also known as Insulin-degrading enzyme (IDE), is a highly conserved zinc metallopeptidase that contains an inverted zincin motif (HXXEH), characteristic of the inverzincin family of proteases. The two histidine (H) residues chelate with the zinc ion, and the glutamate (E) is involved in catalytic water activation. Insulysin functions as a dimer and exhibits allosteric kinetics, whereby small substrate peptides and polyphosphates such as ATP can act as enzyme activators. The endopeptidase cleaves a wide variety of substrates that are diverse in length, structure and sequence and exhibits a preference for basic or bulky hydrophobic residues.

    Insulysin was initially discovered as the enzyme responsible for insulin catabolism and is ubiquitously expressed; studies have shown that it is involved in the degradation of many bioactive peptide substrates including glucagon, TGF-α, β-endorphin, dynorphins and atrial natriuretic peptide. Insulysin also selectively degrades amylin and β-amyloid amyloidogenic peptides at multiple sites. The imbalance between synthesis and clearance of β-amyloid peptides can lead to the accumulation and formation of amyloid plaques in the brain, which is one of the hallmarks of Alzheimer’s disease. Insulysin is a key component in the maintenance of proteostasis in many cellular processes, therefore the identification of novel potent and selective insulysin modulators can help advance the development of insulysin-based therapeutics for diseases such as type 2 diabetes and Alzheimer's Disease.

    Unravelling the effects of insulysin modulators on the multiplicity of insulysin targets will provide an insight of its pivotal role in interconnecting several cellular processes.


    Available to purchase through DISCOVERY® Peptides

    Insulysin FRET substrate [Mca]/[Dnp]


    catalogue number: crb1100406


  • Peptide Substrates: Focus on LRRKtide

    Mutations in the Leucine-rich repeat kinase-2 (LRRK2) gene have been associated with familial and sporadic Parkinson’s disease (PD), which is the second most common neurodegenerative disorder worldwide after Alzheimer’s. LRRK2 is a multi-domain protein that contains an LRR (leucine rich repeats) motif, a COR (C-terminal of Ras of Complex) domain, a WD40 (Trp-Asp 40) motif and two distinct functional domains; a GTPase domain and a protein kinase domain. The majority of pathological mutations in LRRK2 are clustered within the three domains that form the enzymatic core. The most prevalent mutant form of LRRK2 is the Gly2019Ser mutation, which up-regulates LRRK2 kinase activity. Gly2019 is located within the Asp-Tyr-Gly-Mg2+-binding motif of the kinase domain.

    Moesin was identified as a physiological substrate of LRRK2 in a kinase substrate tracking and elucidation (KESTREL) screen using rat brain extracts. Belonging to the ezrin/redixin/moesin ERM family of proteins, Moesin functions as an anchor between actin-based cytoskeletons and plasma membranes. Analysis of radiolabelled phosphopeptides, derived from LRRK2 phosphorylated Moesin, mapped Thr558 as a phosphorylation site. LRRK2 was also shown to phosphorylate ezrin (Thr567) and radixin (Thr564) at residues equivalent to Moesin Thr558; consequently, the LRRKtide peptide (RLGRDKYKTLRQIRQ) from Moesin that encompasses the Thr558 was derived.  Although LRRKtide contains both threonine and tyrosine residues, LRRK2 acts on LRRKtide predominately as a serine/threonine kinase and not as a tyrosine kinase.

    LRRKtide is widely used for the enzymatic characterization of LRRK2 kinase activity and inhibition studies and is considered to be a more efficient substrate for quantitative assays, compared to measuring LRRK2 auto-phosphorylation. Multiple studies have used LRRKtide to assess the effects of pathogenic mutations on LRRK2 kinase activity and as LRRK2 is clinically linked to PD, LRRK2 kinase has been considered as a therapeutic target. In addition, LRRKtide has been used for comparing the efficiencies of Mg2+ and Mn2+ divalent metal ions as ATP cofactors, to support LRRK2 kinase activity.

    Novel LRRK2 kinase inhibitors have been identified and evaluated from a library of compounds using high-throughput screening that detects LRRKtide phosphorylation using mass spectrometry. The diverse use of LRRKtide has contributed to a better understanding of the role of LRRK2 in Parkinson’s Disease, and provides further possibilities for future investigations into combating the neurodegenerative disorder.






    LRRKtide amide




    Phosphorylated LRRKtide



  • Focus on Myelin Oligodendrocyte Glycoprotein (MOG)

    Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein on the extracellular surface of oligodendrocytes in the outermost lamellae of the myelin sheath. MOG can exist as monomeric and dimeric species. Its extracellular localisation facilitates its functions as a homophilic adhesion receptor, where it plays a role in the completion, compaction and maintenance of the myelin.

    Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disorder of the central nervous system (CNS) characterized by myelin destruction and axonal degeneration. MOG has been identified as a key autoantigen for demyelination in MS and experimental autoimmune encephalomyelitis (EAE), an animal model that resembles MS. Although MOG is a minor component of the CNS, it is highly immunogenic and can stimulate the activation of T-cell and B-cell responses.

    Immunization of rodents with native or recombinant MOG or synthetic MOG derived peptides induces an inflammatory response and initiates an immune response against myelin, causing damage and degeneration of the CNS. A number of MOG peptide fragments have shown to be encephalitogenic determinants, including MOG (1-22), MOG (35-55), MOG (92-106). Crystal structure studies of the MOG extracellular domain in a homodimer complex reveal that residues within the MOG 1-22, 35-55 and 92-106 map onto the face of the β-sheet and participate in the dimerization interface. This suggests a link between the dimeric form of MOG and a failure of immunological tolerance to MOG seen in MS.

    Studies using various MOG derived peptides show that the MOG (35-55) fragment is the most potent encephalitogen and the immunodominant epitope for T cell response.  MOG (35-55) induced EAE models can be used to recapitulate all three MS subtypes, which are relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS). Depending on the MOG (35-55) dose, immunized mice are presented with varying degrees of neuropathogical impairment, immune infiltration, ascending paralysis, demyelinating lesions, axon loss and gliosis in the spinal cord and brain. MOG (35-55) induced EAE models can provide an insight into elucidating the immunopathological mechanism of MS progression and facilitate in the development of novel therapeutics.


    MOG (35-55) acid Mouse, Rat




    MOG (35-55) amide Mouse, Rat




    MOG (92-106) Mouse, Rat



  • Cell Penetrating Peptides: Focus on Arg9

    An Introduction to Cell Penetrating Peptides:

    Due to the hydrophilic nature of the majority of proteins and peptides, they are largely impermeable to cell membranes. Cell Penetrating Peptides (CPP’s) therefore possess a pivotal role in terms of their ability to successfully facilitate cellular uptake of molecular cargos across the cell or plasma membrane. They typically possess a high relative abundance of the positively charged amino acids Arginine and Lysine or possess an alternating pattern of polar and non-polar residues. Various mechanisms by which CPP’s traverse cell membranes have been postulated including endocytosis and direct translocation but their exact mode of action remains unclear and is, to this day, widely investigated.

    Cambridge Research Biochemicals offer a range of CPP’s through the Discovery Peptides catalogue - more information is given below

    Focus on Arg9

    Arg9 is a synthetic homopolyarginine nona-peptide (R9) cell penetrating peptide (CPP). The arginine amino acids play an important role in efficient cellular uptake. The guanidinium group is a critical structural determinant for tight and rapid interactions with cell membrane. The cationic guanidinium group can form electrostatic interactions with anionic cell membranes components such as phospholipids and sulphated proteoglycans. This interaction can trigger the activation of specific intracellular signalling and cell internalization via various pathways.

    The hydrophilic arginine amino acids destabilize and disrupt the phospholipid bilayer and nucleate transient pores for passive diffusion across the membrane. In addition, the extended 3 carbon linear chain of arginine facilitates insertion and cell permeation. In the presence of different types of phospholipids Arg9 exhibits structural polymorphism with no interfacial properties or specific secondary structure, which implicates endocytosis as another mechanism of cellular uptake. However, the specific endocytosis pathways utilized is dependent on multiple factors such as peptide concentration, environmental conditions and membrane composition. Cell viability and membrane integrity studies of Arg9 peptide intracellular delivery were shown to have low cytotoxicity, no leakage or liposome bilayer entrapment.

    Oligo-arginine peptides have been used to deliver a variety of functionally active cargos such as peptides, small interfering RNA, oligonucleotides, plasmid DNA and liposomes into mammalian cells and plant cells with high translocation efficiency. Non-covalent and covalent strategies have been used to assess cargo delivery. Click Arg9 can be used to form chemical linkages with the cargo and act as a carrier peptide. Understanding the translocation mechanisms of Arg9 can provide an insight in the development of efficient molecular delivery vehicles of drugs and other agents into the cytosol and nucleus of cells.

    Various Arg9 peptides are available via the new Discovery Peptides Catalogue:

    Click on the corresponding catalogue number to be taken to the Discovery webpage:

    Standard unmodified Peptide: Arg9 - Catalogue Number: crb1000182

    5-carboxyfluoroscein labelled Arg9: [5-Fam]-Arg9 - Catalogue Number: crb1100289

    4-pentynyl "Click" functionalised Arg9: Click Arg9 - Catalogue Number: crb1000111

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