Table 1.

Overview of methods of chemical–biological hybrid polymer synthesis indicated along with outcomes.

Synthesis	Type of polymer	Impact	Outcome/merits or demerits	Ref.
Bio-organic homopolymers
Controlled radical,  atom transfer  radical, ring  opening  polymerization	Polypeptides		Demerits-chain breaking and termination reactions, precipitation of the growing polypeptide chain at a certain molecular weight, and formation of unwanted secondary structures making it difficult to prepare homo polypeptides with defined molecular weights and low polydispersity indices	[11–13]
Catalyzed  enzymatic  polymerization	Polysaccharides		Synthesized polysaccharides treated with enzyme allow for living polymerization with predictable molecular weight, Poisson molecular weight distribution	[169,170]
Sequenced bio-organic polymers
Recombinant  DNA	Peptide polymers	Site specific incorporation of unnatural amino acids at any position by using either chemically acylated transfer-RNA (tRNA), or engineered tRNAs and synthetases; unique codons encode for glycosylated amino acids, and amino acids with keto, azido, acetylenic and heavy atom containing side chain	Fidelity in high molecular weight monodisperse	[26,171,172]
Solid phase  peptide  synthesis		Overcomes a number of difficulties related to the selectivity of chemical reactions, the insolubility of protected peptides, the optimization of the applied polymer supports concerning accessibility, diffusion properties and non-specific interactions with the peptide, as well as the difficulty to drive the step-wise reaction to quantitative conversion	Sequence-specific incorporation of unnatural amino acids by chemical synthesis is virtually unlimited. It allows versatile modifications of the peptides (ranging from single position mutants, where one amino acid is substituted, to the synthesis of pseudo-peptides comprising of non peptidic backbones) and their chemistry	[173,174]
Ligation  (native,  coupling)		Diverse selective coupling reactions, adapted from peptide ligation, were used such as formation of thioesters, oximes, thiazolidine/oxazolidine, thioether, and disulfides to attach polymers to peptides		[175,176]
Templated  polymerization	DNA polymers	Programmable interconnections to guide structure formation processes in synthetic polymers for the preparation of materials with preconceived architectural parameters and new properties; enormous potential of oligonucleotides in biodiagnostics	Demerits – Rapid degradation by DNAses, low solubility	[177–179]
	PNA polymers	Stability/tolerance to pH, ionic strengths, expensive synthesis	Pharmacological potential to hybridize with DNA/RNA	[180,181]