The disadvantage of small molecule drugs is that they have poor target selectivity which results in a broad range of side effects. The larger molecule-based
drugs have an advantage of target specificity, majorly based on their biological
characteristics, but the disadvantage of these molecules is their lesser bioavailability
and metabolism. There is a great deal of research in the search of peptide drugs
which lie between the extreme end of the molecular weight spectrum and possess
the advantages of both.
Small molecules are identified from screening, ligand-based, structure-based, or
receptor-based design, and such small molecules were majorly subject of research
with major successes in the treatment of diseases. With advent of molecular biology, purification, and biophysical characterization, new classes of specific molecules were discovered which are named “Biologics.” These are usually antibiotics,
growth factors, insulin substitute, etc., yet these are intravenously administered.
Molecules which are presently in market such as infliximab to treat arthritis,
bevacizumab in treating colorectal cancer, and trastuzumab for breast cancer,
insulin for diabetes, Epogen and Avonex are few peptide-based molecules which
have a high pharmaceutical importance and a financial market. The market for
peptide-based drugs is around $40 billion yearly.
The development of sequencing techniques and analyzing the large datasets of
genes, proteins, and also transcription products had resulted in the identification of
many molecules which are proteins in nature that exhibit specificity toward receptors
and drug targets. Majority of these molecules do not come under the spectrum of
rule-of-five. In addition to this deviation, these peptide-based molecules are metabolized easily by the proteases present in the body rapidly. They have large limitation to
cross the membrane because of the size and others. In spite of these prominent
disadvantages, they possess high efficiency in selective binding and are strong and
natural binders of multiple targets. They are found to accumulate less compared to
synthetic compounds and finally less toxic. Most of the peptides used in pharmaceuticals belong mostly to size lesser than 10 amino acids, with few exceptions. Some
of the peptides which are at the high end of molecular spectrum are 32-residue-long
calcitonin, 34- and 36-residue-long teriparatide and Fuzeon, respectively. Food and
Drug Administration (FDA) has approved about 60 peptide drugs into market, about
140 are under clinical trials, and around 500 are in the stage of preclinical trials [150].
It is interesting to note that recent peptide molecules out in the industry are
exenatide and ziconotide. Exenatide is a 39-residue peptide employed in the diabetes treatment, isolated from saliva of lizard [151]. Ziconotide is isolated from
marine cone snail and targets pain relief. In addition, other low molecular peptides,
such as captopril and tirofiban (3 aa) and eptifibatide (7 aa), isolated from venom of
animals are marketed. Different organisms, namely reptiles, marine fishes, marine
plants, are rich with peptides of moderate size, and they play crucial role in binding
with many neural and inflammatory-related targets. In addition, venom of them
constitutes of various membrane-binding and pore-forming peptides that can act as
anti-bacterial and antifungal agents. Design of peptide with important functional
scaffold is an important approach which helps in producing bioactive mimicking
sequences. Many such scaffolds like knottins, cyclotides [152–155], conotoxins
288
D. Velmurugan et al.
drugs have an advantage of target specificity, majorly based on their biological
characteristics, but the disadvantage of these molecules is their lesser bioavailability
and metabolism. There is a great deal of research in the search of peptide drugs
which lie between the extreme end of the molecular weight spectrum and possess
the advantages of both.
Small molecules are identified from screening, ligand-based, structure-based, or
receptor-based design, and such small molecules were majorly subject of research
with major successes in the treatment of diseases. With advent of molecular biology, purification, and biophysical characterization, new classes of specific molecules were discovered which are named “Biologics.” These are usually antibiotics,
growth factors, insulin substitute, etc., yet these are intravenously administered.
Molecules which are presently in market such as infliximab to treat arthritis,
bevacizumab in treating colorectal cancer, and trastuzumab for breast cancer,
insulin for diabetes, Epogen and Avonex are few peptide-based molecules which
have a high pharmaceutical importance and a financial market. The market for
peptide-based drugs is around $40 billion yearly.
The development of sequencing techniques and analyzing the large datasets of
genes, proteins, and also transcription products had resulted in the identification of
many molecules which are proteins in nature that exhibit specificity toward receptors
and drug targets. Majority of these molecules do not come under the spectrum of
rule-of-five. In addition to this deviation, these peptide-based molecules are metabolized easily by the proteases present in the body rapidly. They have large limitation to
cross the membrane because of the size and others. In spite of these prominent
disadvantages, they possess high efficiency in selective binding and are strong and
natural binders of multiple targets. They are found to accumulate less compared to
synthetic compounds and finally less toxic. Most of the peptides used in pharmaceuticals belong mostly to size lesser than 10 amino acids, with few exceptions. Some
of the peptides which are at the high end of molecular spectrum are 32-residue-long
calcitonin, 34- and 36-residue-long teriparatide and Fuzeon, respectively. Food and
Drug Administration (FDA) has approved about 60 peptide drugs into market, about
140 are under clinical trials, and around 500 are in the stage of preclinical trials [150].
It is interesting to note that recent peptide molecules out in the industry are
exenatide and ziconotide. Exenatide is a 39-residue peptide employed in the diabetes treatment, isolated from saliva of lizard [151]. Ziconotide is isolated from
marine cone snail and targets pain relief. In addition, other low molecular peptides,
such as captopril and tirofiban (3 aa) and eptifibatide (7 aa), isolated from venom of
animals are marketed. Different organisms, namely reptiles, marine fishes, marine
plants, are rich with peptides of moderate size, and they play crucial role in binding
with many neural and inflammatory-related targets. In addition, venom of them
constitutes of various membrane-binding and pore-forming peptides that can act as
anti-bacterial and antifungal agents. Design of peptide with important functional
scaffold is an important approach which helps in producing bioactive mimicking
sequences. Many such scaffolds like knottins, cyclotides [152–155], conotoxins
288
D. Velmurugan et al.