5 FAQs of Peptide R&D - Omizzur

What are Peptides? What Are Its Characteristics?

Peptides are a class of compounds composed of amino acids connected by peptide bonds,
and are commonly found as chemically active substances in living organisms.

According to the classification system commonly used in the international pharmaceutical

community, drugs with a number of amino acid molecules greater than 100 belong to
protein drugs, while amino acid molecules less than 100 belong to peptide drugs.

According to public information, peptide drugs have advantages such as strong stability,
high selectivity, and low side effects. In clinical applications, peptide drugs mimic the
physiological effects of ligands by acting on receptors on the surface of cell membranes,
thereby exerting their pharmacological effects.

Its structure has high similarity with real physiological active molecules, good specificity and
selectivity, and its efficacy is significantly improved compared to small molecules. The
general daily dosage is a very low concentration between μg-mg can have a good effect.

In addition, peptide drugs are easily hydrolyzed by proteolytic enzymes in plasma, with a
short plasma half-life and therefore do not have drug accumulation effects; In addition,
peptides are mainly cleared through protein hydrolysis degradation and renal filtration, and
the hydrolyzed products are amino acids. Therefore, it is generally not considered whether
the metabolites of peptide drugs are toxic and have good safety.
Generally speaking, peptide drugs typically have high target affinity and have a low risk of off
target. Moreover, compared to recombinant proteins and monoclonal antibodies, peptide
drugs have advantages such as low immunogenicity, convenient preservation, and easy
patent protection.

How are Peptides Synthesized?

Peptide synthesis (peptide chain synthesis) essentially involves arranging amino acid units
according to the structural rules of natural amino acids. To synthesize peptides in a specific
order, the directed peptide synthesis method can only be used, which involves protecting
the amino or carboxyl groups that do not require a reaction with appropriate groups before
proceeding with the linking reaction.

At present, the main methods for peptide synthesis are chemical and biological methods.
The biosynthesis of peptides mainly involves fermentation and enzymatic hydrolysis. With
the development of biotechnology, genetic engineering methods led by DNA recombination
technology have also been applied to the synthesis of peptides.

In the 1980s, almost all clinical trial stages had peptides with lengths less than 10 amino acids.
In the following decade, the average length of peptides gradually increased, mainly due to
the improvement and maturity of peptide synthesis technology. At present, long peptide
chains up to 40 amino acids have also been successfully developed, indicating that peptide
chain length is no longer a challenge in peptide drug development.

From natural extraction to artificial synthesis, peptides, as a new class of drugs, have shown
unique advantages in clinical application and production preparation.
Firstly, in clinical practice, it is similar to recombinant protein drugs and monoclonal
antibodies, with advantages such as strong specificity and good efficacy; Secondly, peptide
drugs are similar in production and preparation to small molecule drugs, with characteristics
such as high purity, controllable quality, and easy determination of structure. Therefore,
peptide therapy is currently considered a highly selective, effective, and relatively safe
potential therapy.

What are the Pathways of Peptide Administration?

Traditional peptide drugs, due to their instability at room temperature and easy degradation
in the body, are mostly used as injections, especially intravenous injection or intravenous drip.
The main type of preparation is freeze-dried powder.

In recent years, with the development of various drug delivery systems, researchers have
developed various types of peptide drugs, presenting multiple delivery pathways.

1 Peptide dosage form

The current peptide drug formulations on the market include microspheres, implants,
liposome microemulsion nanoparticles, etc.

2. Peptide drug delivery pathways

There are mainly two types of medication: injection and non injection. The former includes
intravenous injection, subcutaneous injection, and intramuscular injection, while the latter
includes oral, nasal, ocular, sublingual, percutaneous, pulmonary, rectal, vaginal
administration, etc.

Compared to other administration methods, patients tend to prefer oral administration, but
due to the low oral bioavailability of peptide molecules, most of them still rely on injection
administration.
At present, there are a few peptide drugs administered orally, such as bacitracin, cyclosporin,
linalopide, etc. These drugs have relatively stable peptide structures, mostly cyclic peptides.
The nasal administration method is simple, and there are abundant capillaries in the nasal
cavity, with epithelial cells having active absorption function. Therefore, nasal administration
has become one of the ideal delivery routes.

Nasal spray is the main peptide preparation for nasal administration in clinical use, such as
calcitonin, buserelin, etc. With the emergence of new generation absorption enhancers (alkyl
sugars, PEG modified fatty acids, etc.), new peptide drug nasal delivery formulations have
been developed, and some have entered clinical trials

What are the Drawbacks of Peptides? How Can We

Improve it?

Although peptide therapy has promising prospects, it is not flawless either. Due to the
presence of peptidases, the half-life of peptide hormones is usually short, and this instability
has a negative impact on drug development and treatment.

Peptide molecules have poor stability in living organisms because the amide bonds on their
molecules, especially on their surfaces, are easily recognized and hydrolyzed by proteases.
Therefore, many studies are committed to modifying its structure. As the amino acids
recognized by proteases in the body are natural L-type amino acids, it is possible to replace
the C-end and N-end amino acids of the polypeptide chain with D-type amino acids, or to
change some or all amino acids in the polypeptide chain to D-type amino acids.

Another technical bottleneck of peptide drugs is the low oral utilization rate. In recent years,
a new peptide synthesis strategy has emerged to overcome the aforementioned technical
challenges. Researchers can reduce the injection frequency of peptide drugs and improve
their stability and other physical properties by adjusting pharmacokinetic characteristics,
modifying amino acid frameworks, incorporating non natural amino acids, conjugating
groups that extend half-life, and improving solubility.

What are the Future Developments of Peptides?

Due to the advantages and potential market value of peptides as drugs, the research and
development of peptide drugs has been booming in recent years. However, with the
deepening of research and development, significant progress has been made in the
discovery of target sites, structural modification optimization, and delivery pathways of
peptide drugs. What is the future development direction? Perhaps there is great potential in
the future in areas such as cell penetrating peptides, peptide coupled drugs, and formulation
optimization.

1. Cell penetrating peptide

Cellular transmembrane peptides are a type of peptide composed of usually no more than
30 amino acid residues that can directly penetrate the cell membrane and enter the cell.
They can successfully carry active substances (such as small molecule drugs, siRNAs,
nanoparticles, etc.) into cells to exert their effects.

Cell penetrating peptides can effectively promote the transdermal absorption of biological
macromolecular drugs, and have significant value in targeted formulations, transdermal
delivery formulations, and cosmetics, significantly improving the bioavailability of drugs.

2. Peptide conjugated drugs

Fusion of peptides with binding ability with cytotoxic or cytokines, directing them to the
lesion site, exerting therapeutic effects while reducing toxic side effects. Many toxins,
cytokines, and others are known to have strong tumor cell toxicity, but they can also damage
normal cells.
By fusing peptides that can specifically bind to tumor cells with these active factors, these
active factors can be specifically concentrated at the tumor site, greatly reducing the
concentration of toxins and cytokines used, and reducing damage to normal cells.

3. Formulation optimization
Due to the physical and chemical properties of peptides themselves, most of them are
injection based, especially intravenous injection or intravenous drip. Improving the delivery
method of peptide drugs has become the direction of next-generation peptide drug
research and development.

Therefore, in recent years, in addition to classic subcutaneous, muscular, and intravenous

administration, other delivery routes have gradually developed, including mucosal delivery
(such as nasal, pulmonary, or sublingual), oral delivery, and transdermal delivery.
About Omizzur Biotech
Omizzur is a company engaged in customized synthesis of peptides and impurities,
providing customized services to pharmaceutical R&D companies around the world.

Popular products include exenatide, semaglutide, salmon calcitonin, octreotide, liraglutide,

API and impurities etc.

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