Hydrophilic segments

Historically, after the development of oligopeptide-based vesicles, several groups developed and characterized vesicles using polypeptide hybrid systems consisting of polypeptide and synthetic polymer blocks [17-19]. Soon thereafter, vesicles formed entirely from polypeptides, such as poly(L-lysine)-h-poly(L-leucine) and poly(L-lysine)-h-poly(L-glutamate), were developed [20, 21]. This review will focus on recent developments in the formation of vesicles composed of polypeptide hybrid or polypeptide systems, as well as the potential promise of these systems as effective dmg delivery vehicles. A specific example of a polypeptide-based vesicle is shown in Fig. 1, where the hydrophobic segment is a-helical and the hydrophilic segment is a random coil. 

Fig. 1 Vesicle construct formed from poly(L-lysine)-i)-poly(L-leucme) polypeptides where the poly(L-leucine) block corresponds to the a-helical hydrophobic segments and the poly (L-lysine) block corresponds to the random coil hydrophilic segments. Note that this is one specific example and not all vesicle constructs have a-helical and random coil blocks. Moreover, the amphiphilic copolymer can be comprised of either a pure block copolypeptide or a macromolecule consisting of a polypeptide and another type of polymer. Adapted from [20] with permission. Copyright 2010 American Chemical Society...

Akagi T, Baba M, Akashi M (2007) Preparation of nanoparticles by the self-organization of polymers consisting of hydrophobic and hydrophilic segments potential applications. Polymer 48 6729-6747... 

In addition to the hydrophobic interaction mentioned above to encapsulate guest molecules, other types of nonspecific interactions have also been explored to enhance binding. For example, block copolymer micelles based on PEO as hydrophilic segments and poly(/3-benzyl L-aspartate) as hydrophobic blocks have used to encapsulate doxombicin. The encapsulation efficiency of doxombicin, an aromatic anticancer drug molecule, has been found to be significantly higher. This observation has been attributed to the tt-tt interaction between the anthracycUne moiety of doxorubicin and the benzyl group of poly(/3-benzyl L-aspartate) (Cammas-Marion et al. 1999). 

Fig. 44a. Side group spacer (hydrophilic segments), b Main chain spacer (hydrophilic comonomers), c Main chain spacer and side group spacer (spacer combination) [346]...

Fig. 3 Typical snapshots of the globular conformations of a protein-like, b random, and c random-block copolymers of the same length (N = 512). Hydrophobic segments are shown in light gray and hydrophilic segments in dark gray. Adapted from [18]...

Thus, when the attraction between hydrophilic segments is not sufficiently strong, we deal with the descending branch of the evolution, which leads to nonprotein-like sequences having low information content and low complexity. On the other hand, in the second regime (at epp > epp) the complexity of protein-like structures is found to increase and therefore we have the ascending branch of the evolution. 

Fig. 11 a Mean square gyration radius and b Jensen-Shannon divergence measure as a function of the attraction energy pp between hydrophilic segments, after the sequence evolution procedure. The characteristic energy of H - H interactions is fixed at hh = 2/cbT, thus stabilizing a dense globular core. Adapted from [70]... 

Fig. 13 Radial distribution of hydrophobic and hydrophilic segments (with respect to the center of the globule) for a copolymer chain of 512 segments with a 1 1 HP composition. o is the size of the chain segment. Adapted from [76]...

Fig. 14 Typical core-shell microsegregated structure that is obtained via conformation-dependent copolymerization with simultaneous globule formation in a selective solvent [76]. Hydrophobic chain segments are shown in dark gray and hydrophilic segments are shown in light gray...

Another method leading to nonaggregating copolymers may be connected with the molecular design of their monomeric units. We have discussed an extended variant of the HP model, the HA side-chain model [97], that explicitly takes into account the amphiphilic nature of hydrophilic segments. 

The observed values of the layer thickness and the occupied area can indicate that the hydrophobic segments, which lie essentially flat on the water surface at low surface pressures, aggregate at higher pressures, forming a thicker layer with hydrophobic and hydrophilic segments microphase - separated at the air - water interface. This behavior can be illustrated in Figs. 3.26 [129] and 3.27 [130] for different diblock copolymers. 

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